%0 Journal Article %J Nat Genet %D 2021 %T The trans-ancestral genomic architecture of glycemic traits. %A Chen, Ji %A Spracklen, Cassandra N %A Marenne, Gaëlle %A Varshney, Arushi %A Corbin, Laura J %A Luan, Jian'an %A Willems, Sara M %A Wu, Ying %A Zhang, Xiaoshuai %A Horikoshi, Momoko %A Boutin, Thibaud S %A Mägi, Reedik %A Waage, Johannes %A Li-Gao, Ruifang %A Chan, Kei Hang Katie %A Yao, Jie %A Anasanti, Mila D %A Chu, Audrey Y %A Claringbould, Annique %A Heikkinen, Jani %A Hong, Jaeyoung %A Hottenga, Jouke-Jan %A Huo, Shaofeng %A Kaakinen, Marika A %A Louie, Tin %A Marz, Winfried %A Moreno-Macias, Hortensia %A Ndungu, Anne %A Nelson, Sarah C %A Nolte, Ilja M %A North, Kari E %A Raulerson, Chelsea K %A Ray, Debashree %A Rohde, Rebecca %A Rybin, Denis %A Schurmann, Claudia %A Sim, Xueling %A Southam, Lorraine %A Stewart, Isobel D %A Wang, Carol A %A Wang, Yujie %A Wu, Peitao %A Zhang, Weihua %A Ahluwalia, Tarunveer S %A Appel, Emil V R %A Bielak, Lawrence F %A Brody, Jennifer A %A Burtt, Noël P %A Cabrera, Claudia P %A Cade, Brian E %A Chai, Jin Fang %A Chai, Xiaoran %A Chang, Li-Ching %A Chen, Chien-Hsiun %A Chen, Brian H %A Chitrala, Kumaraswamy Naidu %A Chiu, Yen-Feng %A de Haan, Hugoline G %A Delgado, Graciela E %A Demirkan, Ayse %A Duan, Qing %A Engmann, Jorgen %A Fatumo, Segun A %A Gayán, Javier %A Giulianini, Franco %A Gong, Jung Ho %A Gustafsson, Stefan %A Hai, Yang %A Hartwig, Fernando P %A He, Jing %A Heianza, Yoriko %A Huang, Tao %A Huerta-Chagoya, Alicia %A Hwang, Mi Yeong %A Jensen, Richard A %A Kawaguchi, Takahisa %A Kentistou, Katherine A %A Kim, Young Jin %A Kleber, Marcus E %A Kooner, Ishminder K %A Lai, Shuiqing %A Lange, Leslie A %A Langefeld, Carl D %A Lauzon, Marie %A Li, Man %A Ligthart, Symen %A Liu, Jun %A Loh, Marie %A Long, Jirong %A Lyssenko, Valeriya %A Mangino, Massimo %A Marzi, Carola %A Montasser, May E %A Nag, Abhishek %A Nakatochi, Masahiro %A Noce, Damia %A Noordam, Raymond %A Pistis, Giorgio %A Preuss, Michael %A Raffield, Laura %A Rasmussen-Torvik, Laura J %A Rich, Stephen S %A Robertson, Neil R %A Rueedi, Rico %A Ryan, Kathleen %A Sanna, Serena %A Saxena, Richa %A Schraut, Katharina E %A Sennblad, Bengt %A Setoh, Kazuya %A Smith, Albert V %A Sparsø, Thomas %A Strawbridge, Rona J %A Takeuchi, Fumihiko %A Tan, Jingyi %A Trompet, Stella %A van den Akker, Erik %A van der Most, Peter J %A Verweij, Niek %A Vogel, Mandy %A Wang, Heming %A Wang, Chaolong %A Wang, Nan %A Warren, Helen R %A Wen, Wanqing %A Wilsgaard, Tom %A Wong, Andrew %A Wood, Andrew R %A Xie, Tian %A Zafarmand, Mohammad Hadi %A Zhao, Jing-Hua %A Zhao, Wei %A Amin, Najaf %A Arzumanyan, Zorayr %A Astrup, Arne %A Bakker, Stephan J L %A Baldassarre, Damiano %A Beekman, Marian %A Bergman, Richard N %A Bertoni, Alain %A Blüher, Matthias %A Bonnycastle, Lori L %A Bornstein, Stefan R %A Bowden, Donald W %A Cai, Qiuyin %A Campbell, Archie %A Campbell, Harry %A Chang, Yi Cheng %A de Geus, Eco J C %A Dehghan, Abbas %A Du, Shufa %A Eiriksdottir, Gudny %A Farmaki, Aliki Eleni %A Frånberg, Mattias %A Fuchsberger, Christian %A Gao, Yutang %A Gjesing, Anette P %A Goel, Anuj %A Han, Sohee %A Hartman, Catharina A %A Herder, Christian %A Hicks, Andrew A %A Hsieh, Chang-Hsun %A Hsueh, Willa A %A Ichihara, Sahoko %A Igase, Michiya %A Ikram, M Arfan %A Johnson, W Craig %A Jørgensen, Marit E %A Joshi, Peter K %A Kalyani, Rita R %A Kandeel, Fouad R %A Katsuya, Tomohiro %A Khor, Chiea Chuen %A Kiess, Wieland %A Kolcic, Ivana %A Kuulasmaa, Teemu %A Kuusisto, Johanna %A Läll, Kristi %A Lam, Kelvin %A Lawlor, Deborah A %A Lee, Nanette R %A Lemaitre, Rozenn N %A Li, Honglan %A Lin, Shih-Yi %A Lindström, Jaana %A Linneberg, Allan %A Liu, Jianjun %A Lorenzo, Carlos %A Matsubara, Tatsuaki %A Matsuda, Fumihiko %A Mingrone, Geltrude %A Mooijaart, Simon %A Moon, Sanghoon %A Nabika, Toru %A Nadkarni, Girish N %A Nadler, Jerry L %A Nelis, Mari %A Neville, Matt J %A Norris, Jill M %A Ohyagi, Yasumasa %A Peters, Annette %A Peyser, Patricia A %A Polasek, Ozren %A Qi, Qibin %A Raven, Dennis %A Reilly, Dermot F %A Reiner, Alex %A Rivideneira, Fernando %A Roll, Kathryn %A Rudan, Igor %A Sabanayagam, Charumathi %A Sandow, Kevin %A Sattar, Naveed %A Schürmann, Annette %A Shi, Jinxiu %A Stringham, Heather M %A Taylor, Kent D %A Teslovich, Tanya M %A Thuesen, Betina %A Timmers, Paul R H J %A Tremoli, Elena %A Tsai, Michael Y %A Uitterlinden, Andre %A van Dam, Rob M %A van Heemst, Diana %A van Hylckama Vlieg, Astrid %A Van Vliet-Ostaptchouk, Jana V %A Vangipurapu, Jagadish %A Vestergaard, Henrik %A Wang, Tao %A Willems van Dijk, Ko %A Zemunik, Tatijana %A Abecasis, Gonçalo R %A Adair, Linda S %A Aguilar-Salinas, Carlos Alberto %A Alarcón-Riquelme, Marta E %A An, Ping %A Aviles-Santa, Larissa %A Becker, Diane M %A Beilin, Lawrence J %A Bergmann, Sven %A Bisgaard, Hans %A Black, Corri %A Boehnke, Michael %A Eric Boerwinkle %A Böhm, Bernhard O %A Bønnelykke, Klaus %A Boomsma, D I %A Bottinger, Erwin P %A Buchanan, Thomas A %A Canouil, Mickaël %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der Ida %A Cheng, Ching-Yu %A Collins, Francis S %A Correa, Adolfo %A Cucca, Francesco %A de Silva, H Janaka %A Dedoussis, George %A Elmståhl, Sölve %A Evans, Michele K %A Ferrannini, Ele %A Ferrucci, Luigi %A Florez, Jose C %A Franks, Paul W %A Frayling, Timothy M %A Froguel, Philippe %A Gigante, Bruna %A Goodarzi, Mark O %A Gordon-Larsen, Penny %A Grallert, Harald %A Grarup, Niels %A Grimsgaard, Sameline %A Groop, Leif %A Gudnason, Vilmundur %A Guo, Xiuqing %A Hamsten, Anders %A Hansen, Torben %A Hayward, Caroline %A Heckbert, Susan R %A Horta, Bernardo L %A Huang, Wei %A Ingelsson, Erik %A James, Pankow S %A Jarvelin, Marjo-Ritta %A Jonas, Jost B %A Jukema, J Wouter %A Kaleebu, Pontiano %A Kaplan, Robert %A Kardia, Sharon L R %A Kato, Norihiro %A Keinanen-Kiukaanniemi, Sirkka M %A Kim, Bong-Jo %A Kivimaki, Mika %A Koistinen, Heikki A %A Kooner, Jaspal S %A Körner, Antje %A Kovacs, Peter %A Kuh, Diana %A Kumari, Meena %A Kutalik, Zoltán %A Laakso, Markku %A Lakka, Timo A %A Launer, Lenore J %A Leander, Karin %A Li, Huaixing %A Lin, Xu %A Lind, Lars %A Lindgren, Cecilia %A Liu, Simin %A Loos, Ruth J F %A Magnusson, Patrik K E %A Mahajan, Anubha %A Metspalu, Andres %A Mook-Kanamori, Dennis O %A Mori, Trevor A %A Munroe, Patricia B %A Njølstad, Inger %A O'Connell, Jeffrey R %A Oldehinkel, Albertine J %A Ong, Ken K %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Palmer, Nicholette D %A Pedersen, Oluf %A Pennell, Craig E %A Porteous, David J %A Pramstaller, Peter P %A Province, Michael A %A Psaty, Bruce M %A Qi, Lu %A Raffel, Leslie J %A Rauramaa, Rainer %A Redline, Susan %A Ridker, Paul M %A Rosendaal, Frits R %A Saaristo, Timo E %A Sandhu, Manjinder %A Saramies, Jouko %A Schneiderman, Neil %A Schwarz, Peter %A Scott, Laura J %A Selvin, Elizabeth %A Sever, Peter %A Shu, Xiao-Ou %A Slagboom, P Eline %A Small, Kerrin S %A Smith, Blair H %A Snieder, Harold %A Sofer, Tamar %A Sørensen, Thorkild I A %A Spector, Tim D %A Stanton, Alice %A Steves, Claire J %A Stumvoll, Michael %A Sun, Liang %A Tabara, Yasuharu %A Tai, E Shyong %A Timpson, Nicholas J %A Tonjes, Anke %A Tuomilehto, Jaakko %A Tusie, Teresa %A Uusitupa, Matti %A van der Harst, Pim %A van Duijn, Cornelia %A Vitart, Veronique %A Vollenweider, Peter %A Vrijkotte, Tanja G M %A Wagenknecht, Lynne E %A Walker, Mark %A Wang, Ya X %A Wareham, Nick J %A Watanabe, Richard M %A Watkins, Hugh %A Wei, Wen B %A Wickremasinghe, Ananda R %A Willemsen, Gonneke %A Wilson, James F %A Wong, Tien-Yin %A Wu, Jer-Yuarn %A Xiang, Anny H %A Yanek, Lisa R %A Yengo, Loic %A Yokota, Mitsuhiro %A Zeggini, Eleftheria %A Zheng, Wei %A Zonderman, Alan B %A Rotter, Jerome I %A Gloyn, Anna L %A McCarthy, Mark I %A Dupuis, Josée %A Meigs, James B %A Scott, Robert A %A Prokopenko, Inga %A Leong, Aaron %A Liu, Ching-Ti %A Parker, Stephen C J %A Mohlke, Karen L %A Langenberg, Claudia %A Wheeler, Eleanor %A Morris, Andrew P %A Barroso, Inês %K Alleles %K Blood Glucose %K Epigenesis, Genetic %K Gene Expression Profiling %K Genome, Human %K Genome-Wide Association Study %K Glycated Hemoglobin %K Humans %K Multifactorial Inheritance %K Physical Chromosome Mapping %K Quantitative Trait Loci %K Quantitative Trait, Heritable %K White People %X

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

%B Nat Genet %V 53 %P 840-860 %8 2021 Jun %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/34059833?dopt=Abstract %R 10.1038/s41588-021-00852-9 %0 Journal Article %J Nat Genet %D 2019 %T Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution. %A Justice, Anne E %A Karaderi, Tugce %A Highland, Heather M %A Young, Kristin L %A Graff, Mariaelisa %A Lu, Yingchang %A Turcot, Valérie %A Auer, Paul L %A Fine, Rebecca S %A Guo, Xiuqing %A Schurmann, Claudia %A Lempradl, Adelheid %A Marouli, Eirini %A Mahajan, Anubha %A Winkler, Thomas W %A Locke, Adam E %A Medina-Gomez, Carolina %A Esko, Tõnu %A Vedantam, Sailaja %A Giri, Ayush %A Lo, Ken Sin %A Alfred, Tamuno %A Mudgal, Poorva %A Ng, Maggie C Y %A Heard-Costa, Nancy L %A Feitosa, Mary F %A Manning, Alisa K %A Willems, Sara M %A Sivapalaratnam, Suthesh %A Abecasis, Goncalo %A Alam, Dewan S %A Allison, Matthew %A Amouyel, Philippe %A Arzumanyan, Zorayr %A Balkau, Beverley %A Bastarache, Lisa %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boehnke, Michael %A Boeing, Heiner %A Eric Boerwinkle %A Böger, Carsten A %A Bork-Jensen, Jette %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Broer, Linda %A Burt, Amber A %A Butterworth, Adam S %A Caulfield, Mark J %A Cesana, Giancarlo %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der Ida %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Collins, Francis S %A Cook, James P %A Cox, Amanda J %A Crosslin, David S %A Danesh, John %A de Bakker, Paul I W %A Denus, Simon de %A Mutsert, Renée de %A Dedoussis, George %A Demerath, Ellen W %A Dennis, Joe G %A Denny, Josh C %A Di Angelantonio, Emanuele %A Dörr, Marcus %A Drenos, Fotios %A Dube, Marie-Pierre %A Dunning, Alison M %A Easton, Douglas F %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Feng, Shuang %A Ferrannini, Ele %A Ferrieres, Jean %A Florez, Jose C %A Fornage, Myriam %A Fox, Caroline S %A Franks, Paul W %A Friedrich, Nele %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Giedraitis, Vilmantas %A Girotto, Giorgia %A Gorski, Mathias %A Grallert, Harald %A Grarup, Niels %A Grove, Megan L %A Gustafsson, Stefan %A Haessler, Jeff %A Hansen, Torben %A Hattersley, Andrew T %A Hayward, Caroline %A Heid, Iris M %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hu, Yao %A Hung, Yi-Jen %A Hveem, Kristian %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jarvik, Gail P %A Jia, Yucheng %A Jørgensen, Torben %A Jousilahti, Pekka %A Justesen, Johanne M %A Kahali, Bratati %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kee, Frank %A Kitajima, Hidetoshi %A Komulainen, Pirjo %A Kooner, Jaspal S %A Kovacs, Peter %A Krämer, Bernhard K %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lamparter, David %A Lange, Leslie A %A Langenberg, Claudia %A Larson, Eric B %A Lee, Nanette R %A Lee, Wen-Jane %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Dajiang J %A Luan, Jian'an %A Lyytikäinen, Leo-Pekka %A MacGregor, Stuart %A Mägi, Reedik %A Männistö, Satu %A Marenne, Gaëlle %A Marten, Jonathan %A Masca, Nicholas G D %A McCarthy, Mark I %A Meidtner, Karina %A Mihailov, Evelin %A Moilanen, Leena %A Moitry, Marie %A Mook-Kanamori, Dennis O %A Morgan, Anna %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Narisu, Narisu %A Nelson, Christopher P %A Neville, Matt %A Ntalla, Ioanna %A O'Connell, Jeffrey R %A Owen, Katharine R %A Pedersen, Oluf %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Pers, Tune H %A Ewing, Ailith %A Polasek, Ozren %A Raitakari, Olli T %A Rasheed, Asif %A Raulerson, Chelsea K %A Rauramaa, Rainer %A Reilly, Dermot F %A Reiner, Alex P %A Ridker, Paul M %A Rivas, Manuel A %A Robertson, Neil R %A Robino, Antonietta %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo %A Sim, Xueling %A Slater, Andrew J %A Small, Kerrin S %A Smith, Blair H %A Smith, Jennifer A %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Stefansson, Kari %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen E %A Strauch, Konstantin %A Stringham, Heather M %A Stumvoll, Michael %A Sun, Liang %A Surendran, Praveen %A Swart, Karin M A %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tonjes, Anke %A Torres, Mina %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Uitterlinden, André G %A Uusitupa, Matti %A van Duijn, Cornelia M %A Vanhala, Mauno %A Varma, Rohit %A Vermeulen, Sita H %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Vuckovic, Dragana %A Wagenknecht, Lynne E %A Walker, Mark %A Wallentin, Lars %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wareham, Nicholas J %A Warren, Helen R %A Waterworth, Dawn M %A Wessel, Jennifer %A White, Harvey D %A Willer, Cristen J %A Wilson, James G %A Wood, Andrew R %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zheng, He %A Zhou, Wei %A Zillikens, M Carola %A Rivadeneira, Fernando %A Borecki, Ingrid B %A Pospisilik, J Andrew %A Deloukas, Panos %A Frayling, Timothy M %A Lettre, Guillaume %A Mohlke, Karen L %A Rotter, Jerome I %A Kutalik, Zoltán %A Hirschhorn, Joel N %A Cupples, L Adrienne %A Loos, Ruth J F %A North, Kari E %A Lindgren, Cecilia M %K Animals %K Body Fat Distribution %K Body Mass Index %K Case-Control Studies %K Drosophila %K Exome %K Female %K Gene Frequency %K Genetic Predisposition to Disease %K Genetic Variation %K Genome-Wide Association Study %K Homeostasis %K Humans %K Lipids %K Male %K Proteins %K Risk Factors %K Waist-Hip Ratio %X

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

%B Nat Genet %V 51 %P 452-469 %8 2019 Mar %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/30778226?dopt=Abstract %R 10.1038/s41588-018-0334-2 %0 Journal Article %J Nat Genet %D 2019 %T Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. %A Turcot, Valérie %A Lu, Yingchang %A Highland, Heather M %A Schurmann, Claudia %A Justice, Anne E %A Fine, Rebecca S %A Bradfield, Jonathan P %A Esko, Tõnu %A Giri, Ayush %A Graff, Mariaelisa %A Guo, Xiuqing %A Hendricks, Audrey E %A Karaderi, Tugce %A Lempradl, Adelheid %A Locke, Adam E %A Mahajan, Anubha %A Marouli, Eirini %A Sivapalaratnam, Suthesh %A Young, Kristin L %A Alfred, Tamuno %A Feitosa, Mary F %A Masca, Nicholas G D %A Manning, Alisa K %A Medina-Gomez, Carolina %A Mudgal, Poorva %A Ng, Maggie C Y %A Reiner, Alex P %A Vedantam, Sailaja %A Willems, Sara M %A Winkler, Thomas W %A Abecasis, Goncalo %A Aben, Katja K %A Alam, Dewan S %A Alharthi, Sameer E %A Allison, Matthew %A Amouyel, Philippe %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Bang, Lia E %A Barroso, Inês %A Bastarache, Lisa %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boehnke, Michael %A Boeing, Heiner %A Eric Boerwinkle %A Böger, Carsten A %A Bork-Jensen, Jette %A Bots, Michiel L %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Brumat, Marco %A Burt, Amber A %A Butterworth, Adam S %A Campbell, Peter T %A Cappellani, Stefania %A Carey, David J %A Catamo, Eulalia %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der I %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Galbany, Jordi Corominas %A Cox, Amanda J %A Crosslin, David S %A Cuellar-Partida, Gabriel %A D'Eustacchio, Angela %A Danesh, John %A Davies, Gail %A Bakker, Paul I W %A Groot, Mark C H %A Mutsert, Renée %A Deary, Ian J %A Dedoussis, George %A Demerath, Ellen W %A Heijer, Martin %A Hollander, Anneke I %A Ruijter, Hester M %A Dennis, Joe G %A Denny, Josh C %A Di Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dube, Marie-Pierre %A Dunning, Alison M %A Easton, Douglas F %A Edwards, Todd L %A Ellinghaus, David %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Farooqi, I Sadaf %A Faul, Jessica D %A Fauser, Sascha %A Feng, Shuang %A Ferrannini, Ele %A Ferrieres, Jean %A Florez, Jose C %A Ford, Ian %A Fornage, Myriam %A Franco, Oscar H %A Franke, Andre %A Franks, Paul W %A Friedrich, Nele %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Gibson, Jane %A Giedraitis, Vilmantas %A Gjesing, Anette P %A Gordon-Larsen, Penny %A Gorski, Mathias %A Grabe, Hans-Jörgen %A Grant, Struan F A %A Grarup, Niels %A Griffiths, Helen L %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Haessler, Jeff %A Hakonarson, Hakon %A Hammerschlag, Anke R %A Hansen, Torben %A Harris, Kathleen Mullan %A Harris, Tamara B %A Hattersley, Andrew T %A Have, Christian T %A Hayward, Caroline %A He, Liang %A Heard-Costa, Nancy L %A Heath, Andrew C %A Heid, Iris M %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hu, Yao %A Huang, Paul L %A Huffman, Jennifer E %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jia, Yucheng %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kathiresan, Sekar %A Kee, Frank %A Kiemeney, Lambertus A %A Kim, Eric %A Kitajima, Hidetoshi %A Komulainen, Pirjo %A Kooner, Jaspal S %A Kooperberg, Charles %A Korhonen, Tellervo %A Kovacs, Peter %A Kuivaniemi, Helena %A Kutalik, Zoltán %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lamparter, David %A Lange, Ethan M %A Lange, Leslie A %A Langenberg, Claudia %A Larson, Eric B %A Lee, Nanette R %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Keng-Hung %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Dajiang J %A Liu, Yongmei %A Lo, Ken S %A Lophatananon, Artitaya %A Lotery, Andrew J %A Loukola, Anu %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Männistö, Satu %A Marenne, Gaëlle %A Mazul, Angela L %A McCarthy, Mark I %A McKean-Cowdin, Roberta %A Medland, Sarah E %A Meidtner, Karina %A Milani, Lili %A Mistry, Vanisha %A Mitchell, Paul %A Mohlke, Karen L %A Moilanen, Leena %A Moitry, Marie %A Montgomery, Grant W %A Mook-Kanamori, Dennis O %A Moore, Carmel %A Mori, Trevor A %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Nalls, Mike A %A Narisu, Narisu %A Nelson, Christopher P %A Neville, Matt %A Nielsen, Sune F %A Nikus, Kjell %A Njølstad, Pål R %A Nordestgaard, Børge G %A Nyholt, Dale R %A O'Connel, Jeffrey R %A O'Donoghue, Michelle L %A Loohuis, Loes M Olde %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Palmer, Nicholette D %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Pers, Tune H %A Person, Thomas N %A Peters, Annette %A Petersen, Eva R B %A Peyser, Patricia A %A Pirie, Ailith %A Polasek, Ozren %A Polderman, Tinca J %A Puolijoki, Hannu %A Raitakari, Olli T %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Renstrom, Frida %A Rheinberger, Myriam %A Ridker, Paul M %A Rioux, John D %A Rivas, Manuel A %A Roberts, David J %A Robertson, Neil R %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Sapkota, Yadav %A Sattar, Naveed %A Schoen, Robert E %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Shah, Svati H %A Sheu, Wayne H-H %A Sim, Xueling %A Slater, Andrew J %A Small, Kerrin S %A Smith, Albert V %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Starr, John M %A Stefansson, Kari %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen E %A Strauch, Konstantin %A Stringham, Heather M %A Stumvoll, Michael %A Sun, Liang %A Surendran, Praveen %A Swift, Amy J %A Tada, Hayato %A Tansey, Katherine E %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tonjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A Uitterlinden, André G %A Uusitupa, Matti %A Laan, Sander W %A Duijn, Cornelia M %A Leeuwen, Nienke %A van Setten, Jessica %A Vanhala, Mauno %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Edwards, Digna R Velez %A Vermeulen, Sita H %A Veronesi, Giovanni %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Völker, Uwe %A Vuckovic, Dragana %A Wagenknecht, Lynne E %A Walker, Mark %A Wallentin, Lars %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Ware, Erin B %A Wareham, Nicholas J %A Warren, Helen R %A Waterworth, Dawn M %A Wessel, Jennifer %A White, Harvey D %A Willer, Cristen J %A Wilson, James G %A Witte, Daniel R %A Wood, Andrew R %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zhao, Wei %A Zhou, Wei %A Zondervan, Krina T %A Rotter, Jerome I %A Pospisilik, John A %A Rivadeneira, Fernando %A Borecki, Ingrid B %A Deloukas, Panos %A Frayling, Timothy M %A Lettre, Guillaume %A North, Kari E %A Lindgren, Cecilia M %A Hirschhorn, Joel N %A Loos, Ruth J F %X

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

%B Nat Genet %V 51 %P 1191-1192 %8 2019 Jul %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/31160809?dopt=Abstract %R 10.1038/s41588-019-0447-2 %0 Journal Article %J Nat Genet %D 2018 %T Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. %A Turcot, Valérie %A Lu, Yingchang %A Highland, Heather M %A Schurmann, Claudia %A Justice, Anne E %A Fine, Rebecca S %A Bradfield, Jonathan P %A Esko, Tõnu %A Giri, Ayush %A Graff, Mariaelisa %A Guo, Xiuqing %A Hendricks, Audrey E %A Karaderi, Tugce %A Lempradl, Adelheid %A Locke, Adam E %A Mahajan, Anubha %A Marouli, Eirini %A Sivapalaratnam, Suthesh %A Young, Kristin L %A Alfred, Tamuno %A Feitosa, Mary F %A Masca, Nicholas G D %A Manning, Alisa K %A Medina-Gomez, Carolina %A Mudgal, Poorva %A Ng, Maggie C Y %A Reiner, Alex P %A Vedantam, Sailaja %A Willems, Sara M %A Winkler, Thomas W %A Abecasis, Goncalo %A Aben, Katja K %A Alam, Dewan S %A Alharthi, Sameer E %A Allison, Matthew %A Amouyel, Philippe %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Bang, Lia E %A Barroso, Inês %A Bastarache, Lisa %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boehnke, Michael %A Boeing, Heiner %A Eric Boerwinkle %A Böger, Carsten A %A Bork-Jensen, Jette %A Bots, Michiel L %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Brumat, Marco %A Burt, Amber A %A Butterworth, Adam S %A Campbell, Peter T %A Cappellani, Stefania %A Carey, David J %A Catamo, Eulalia %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der I %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Corominas Galbany, Jordi %A Cox, Amanda J %A Crosslin, David S %A Cuellar-Partida, Gabriel %A D'Eustacchio, Angela %A Danesh, John %A Davies, Gail %A Bakker, Paul I W %A Groot, Mark C H %A Mutsert, Renée %A Deary, Ian J %A Dedoussis, George %A Demerath, Ellen W %A Heijer, Martin %A Hollander, Anneke I %A Ruijter, Hester M %A Dennis, Joe G %A Denny, Josh C %A Di Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dube, Marie-Pierre %A Dunning, Alison M %A Easton, Douglas F %A Edwards, Todd L %A Ellinghaus, David %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Farooqi, I Sadaf %A Faul, Jessica D %A Fauser, Sascha %A Feng, Shuang %A Ferrannini, Ele %A Ferrieres, Jean %A Florez, Jose C %A Ford, Ian %A Fornage, Myriam %A Franco, Oscar H %A Franke, Andre %A Franks, Paul W %A Friedrich, Nele %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Gibson, Jane %A Giedraitis, Vilmantas %A Gjesing, Anette P %A Gordon-Larsen, Penny %A Gorski, Mathias %A Grabe, Hans-Jörgen %A Grant, Struan F A %A Grarup, Niels %A Griffiths, Helen L %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Haessler, Jeff %A Hakonarson, Hakon %A Hammerschlag, Anke R %A Hansen, Torben %A Harris, Kathleen Mullan %A Harris, Tamara B %A Hattersley, Andrew T %A Have, Christian T %A Hayward, Caroline %A He, Liang %A Heard-Costa, Nancy L %A Heath, Andrew C %A Heid, Iris M %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hu, Yao %A Huang, Paul L %A Huffman, Jennifer E %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jia, Yucheng %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kathiresan, Sekar %A Kee, Frank %A Kiemeney, Lambertus A %A Kim, Eric %A Kitajima, Hidetoshi %A Komulainen, Pirjo %A Kooner, Jaspal S %A Kooperberg, Charles %A Korhonen, Tellervo %A Kovacs, Peter %A Kuivaniemi, Helena %A Kutalik, Zoltán %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lamparter, David %A Lange, Ethan M %A Lange, Leslie A %A Langenberg, Claudia %A Larson, Eric B %A Lee, Nanette R %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Keng-Hung %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Dajiang J %A Liu, Yongmei %A Lo, Ken S %A Lophatananon, Artitaya %A Lotery, Andrew J %A Loukola, Anu %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Männistö, Satu %A Marenne, Gaëlle %A Mazul, Angela L %A McCarthy, Mark I %A McKean-Cowdin, Roberta %A Medland, Sarah E %A Meidtner, Karina %A Milani, Lili %A Mistry, Vanisha %A Mitchell, Paul %A Mohlke, Karen L %A Moilanen, Leena %A Moitry, Marie %A Montgomery, Grant W %A Mook-Kanamori, Dennis O %A Moore, Carmel %A Mori, Trevor A %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Nalls, Mike A %A Narisu, Narisu %A Nelson, Christopher P %A Neville, Matt %A Nielsen, Sune F %A Nikus, Kjell %A Njølstad, Pål R %A Nordestgaard, Børge G %A Nyholt, Dale R %A O'Connel, Jeffrey R %A O'Donoghue, Michelle L %A Olde Loohuis, Loes M %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Palmer, Nicholette D %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Pers, Tune H %A Person, Thomas N %A Peters, Annette %A Petersen, Eva R B %A Peyser, Patricia A %A Pirie, Ailith %A Polasek, Ozren %A Polderman, Tinca J %A Puolijoki, Hannu %A Raitakari, Olli T %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Renstrom, Frida %A Rheinberger, Myriam %A Ridker, Paul M %A Rioux, John D %A Rivas, Manuel A %A Roberts, David J %A Robertson, Neil R %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Sapkota, Yadav %A Sattar, Naveed %A Schoen, Robert E %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Shah, Svati H %A Sheu, Wayne H-H %A Sim, Xueling %A Slater, Andrew J %A Small, Kerrin S %A Smith, Albert V %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Starr, John M %A Stefansson, Kari %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen E %A Strauch, Konstantin %A Stringham, Heather M %A Stumvoll, Michael %A Sun, Liang %A Surendran, Praveen %A Swift, Amy J %A Tada, Hayato %A Tansey, Katherine E %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tonjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A Uitterlinden, André G %A Uusitupa, Matti %A Laan, Sander W %A Duijn, Cornelia M %A Leeuwen, Nienke %A van Setten, Jessica %A Vanhala, Mauno %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Velez Edwards, Digna R %A Vermeulen, Sita H %A Veronesi, Giovanni %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Völker, Uwe %A Vuckovic, Dragana %A Wagenknecht, Lynne E %A Walker, Mark %A Wallentin, Lars %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Ware, Erin B %A Wareham, Nicholas J %A Warren, Helen R %A Waterworth, Dawn M %A Wessel, Jennifer %A White, Harvey D %A Willer, Cristen J %A Wilson, James G %A Witte, Daniel R %A Wood, Andrew R %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zhao, Wei %A Zhou, Wei %A Zondervan, Krina T %A Rotter, Jerome I %A Pospisilik, John A %A Rivadeneira, Fernando %A Borecki, Ingrid B %A Deloukas, Panos %A Frayling, Timothy M %A Lettre, Guillaume %A North, Kari E %A Lindgren, Cecilia M %A Hirschhorn, Joel N %A Loos, Ruth J F %K Adult %K Animals %K Body Mass Index %K Drosophila %K Energy Intake %K Energy Metabolism %K Female %K Gene Frequency %K Genetic Variation %K Humans %K Male %K Obesity %K Proteins %K Syndrome %X

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

%B Nat Genet %V 50 %P 26-41 %8 2018 Jan %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/29273807?dopt=Abstract %R 10.1038/s41588-017-0011-x %0 Journal Article %J Nat Genet %D 2018 %T Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. %A Turcot, Valérie %A Lu, Yingchang %A Highland, Heather M %A Schurmann, Claudia %A Justice, Anne E %A Fine, Rebecca S %A Bradfield, Jonathan P %A Esko, Tõnu %A Giri, Ayush %A Graff, Mariaelisa %A Guo, Xiuqing %A Hendricks, Audrey E %A Karaderi, Tugce %A Lempradl, Adelheid %A Locke, Adam E %A Mahajan, Anubha %A Marouli, Eirini %A Sivapalaratnam, Suthesh %A Young, Kristin L %A Alfred, Tamuno %A Feitosa, Mary F %A Masca, Nicholas G D %A Manning, Alisa K %A Medina-Gomez, Carolina %A Mudgal, Poorva %A Ng, Maggie C Y %A Reiner, Alex P %A Vedantam, Sailaja %A Willems, Sara M %A Winkler, Thomas W %A Abecasis, Goncalo %A Aben, Katja K %A Alam, Dewan S %A Alharthi, Sameer E %A Allison, Matthew %A Amouyel, Philippe %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Bang, Lia E %A Barroso, Inês %A Bastarache, Lisa %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boehnke, Michael %A Boeing, Heiner %A Eric Boerwinkle %A Böger, Carsten A %A Bork-Jensen, Jette %A Bots, Michiel L %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Brumat, Marco %A Burt, Amber A %A Butterworth, Adam S %A Campbell, Peter T %A Cappellani, Stefania %A Carey, David J %A Catamo, Eulalia %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der I %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Corominas Galbany, Jordi %A Cox, Amanda J %A Crosslin, David S %A Cuellar-Partida, Gabriel %A D'Eustacchio, Angela %A Danesh, John %A Davies, Gail %A Bakker, Paul I W %A Groot, Mark C H %A Mutsert, Renée %A Deary, Ian J %A Dedoussis, George %A Demerath, Ellen W %A Heijer, Martin %A Hollander, Anneke I %A Ruijter, Hester M %A Dennis, Joe G %A Denny, Josh C %A Di Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dube, Marie-Pierre %A Dunning, Alison M %A Easton, Douglas F %A Edwards, Todd L %A Ellinghaus, David %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Farooqi, I Sadaf %A Faul, Jessica D %A Fauser, Sascha %A Feng, Shuang %A Ferrannini, Ele %A Ferrieres, Jean %A Florez, Jose C %A Ford, Ian %A Fornage, Myriam %A Franco, Oscar H %A Franke, Andre %A Franks, Paul W %A Friedrich, Nele %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Gibson, Jane %A Giedraitis, Vilmantas %A Gjesing, Anette P %A Gordon-Larsen, Penny %A Gorski, Mathias %A Grabe, Hans-Jörgen %A Grant, Struan F A %A Grarup, Niels %A Griffiths, Helen L %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Haessler, Jeff %A Hakonarson, Hakon %A Hammerschlag, Anke R %A Hansen, Torben %A Harris, Kathleen Mullan %A Harris, Tamara B %A Hattersley, Andrew T %A Have, Christian T %A Hayward, Caroline %A He, Liang %A Heard-Costa, Nancy L %A Heath, Andrew C %A Heid, Iris M %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hu, Yao %A Huang, Paul L %A Huffman, Jennifer E %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jia, Yucheng %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kathiresan, Sekar %A Kee, Frank %A Kiemeney, Lambertus A %A Kim, Eric %A Kitajima, Hidetoshi %A Komulainen, Pirjo %A Kooner, Jaspal S %A Kooperberg, Charles %A Korhonen, Tellervo %A Kovacs, Peter %A Kuivaniemi, Helena %A Kutalik, Zoltán %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lamparter, David %A Lange, Ethan M %A Lange, Leslie A %A Langenberg, Claudia %A Larson, Eric B %A Lee, Nanette R %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Keng-Hung %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Dajiang J %A Liu, Yongmei %A Lo, Ken S %A Lophatananon, Artitaya %A Lotery, Andrew J %A Loukola, Anu %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Männistö, Satu %A Marenne, Gaëlle %A Mazul, Angela L %A McCarthy, Mark I %A McKean-Cowdin, Roberta %A Medland, Sarah E %A Meidtner, Karina %A Milani, Lili %A Mistry, Vanisha %A Mitchell, Paul %A Mohlke, Karen L %A Moilanen, Leena %A Moitry, Marie %A Montgomery, Grant W %A Mook-Kanamori, Dennis O %A Moore, Carmel %A Mori, Trevor A %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Nalls, Mike A %A Narisu, Narisu %A Nelson, Christopher P %A Neville, Matt %A Nielsen, Sune F %A Nikus, Kjell %A Njølstad, Pål R %A Nordestgaard, Børge G %A Nyholt, Dale R %A O'Connel, Jeffrey R %A O'Donoghue, Michelle L %A Olde Loohuis, Loes M %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Palmer, Nicholette D %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Pers, Tune H %A Person, Thomas N %A Peters, Annette %A Petersen, Eva R B %A Peyser, Patricia A %A Pirie, Ailith %A Polasek, Ozren %A Polderman, Tinca J %A Puolijoki, Hannu %A Raitakari, Olli T %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Renstrom, Frida %A Rheinberger, Myriam %A Ridker, Paul M %A Rioux, John D %A Rivas, Manuel A %A Roberts, David J %A Robertson, Neil R %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Sapkota, Yadav %A Sattar, Naveed %A Schoen, Robert E %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Shah, Svati H %A Sheu, Wayne H-H %A Sim, Xueling %A Slater, Andrew J %A Small, Kerrin S %A Smith, Albert V %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Starr, John M %A Stefansson, Kari %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen E %A Strauch, Konstantin %A Stringham, Heather M %A Stumvoll, Michael %A Sun, Liang %A Surendran, Praveen %A Swift, Amy J %A Tada, Hayato %A Tansey, Katherine E %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tonjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A Uitterlinden, André G %A Uusitupa, Matti %A Laan, Sander W %A Duijn, Cornelia M %A Leeuwen, Nienke %A van Setten, Jessica %A Vanhala, Mauno %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Velez Edwards, Digna R %A Vermeulen, Sita H %A Veronesi, Giovanni %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Völker, Uwe %A Vuckovic, Dragana %A Wagenknecht, Lynne E %A Walker, Mark %A Wallentin, Lars %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Ware, Erin B %A Wareham, Nicholas J %A Warren, Helen R %A Waterworth, Dawn M %A Wessel, Jennifer %A White, Harvey D %A Willer, Cristen J %A Wilson, James G %A Witte, Daniel R %A Wood, Andrew R %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zhao, Wei %A Zhou, Wei %A Zondervan, Krina T %A Rotter, Jerome I %A Pospisilik, John A %A Rivadeneira, Fernando %A Borecki, Ingrid B %A Deloukas, Panos %A Frayling, Timothy M %A Lettre, Guillaume %A North, Kari E %A Lindgren, Cecilia M %A Hirschhorn, Joel N %A Loos, Ruth J F %X

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

%B Nat Genet %V 50 %P 766-767 %8 2018 May %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/29549330?dopt=Abstract %R 10.1038/s41588-018-0082-3 %0 Journal Article %J Nat Genet %D 2018 %T Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. %A Turcot, Valérie %A Lu, Yingchang %A Highland, Heather M %A Schurmann, Claudia %A Justice, Anne E %A Fine, Rebecca S %A Bradfield, Jonathan P %A Esko, Tõnu %A Giri, Ayush %A Graff, Mariaelisa %A Guo, Xiuqing %A Hendricks, Audrey E %A Karaderi, Tugce %A Lempradl, Adelheid %A Locke, Adam E %A Mahajan, Anubha %A Marouli, Eirini %A Sivapalaratnam, Suthesh %A Young, Kristin L %A Alfred, Tamuno %A Feitosa, Mary F %A Masca, Nicholas G D %A Manning, Alisa K %A Medina-Gomez, Carolina %A Mudgal, Poorva %A Ng, Maggie C Y %A Reiner, Alex P %A Vedantam, Sailaja %A Willems, Sara M %A Winkler, Thomas W %A Abecasis, Goncalo %A Aben, Katja K %A Alam, Dewan S %A Alharthi, Sameer E %A Allison, Matthew %A Amouyel, Philippe %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Bang, Lia E %A Barroso, Inês %A Bastarache, Lisa %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boehnke, Michael %A Boeing, Heiner %A Eric Boerwinkle %A Böger, Carsten A %A Bork-Jensen, Jette %A Bots, Michiel L %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Brumat, Marco %A Burt, Amber A %A Butterworth, Adam S %A Campbell, Peter T %A Cappellani, Stefania %A Carey, David J %A Catamo, Eulalia %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der I %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Corominas Galbany, Jordi %A Cox, Amanda J %A Crosslin, David S %A Cuellar-Partida, Gabriel %A D'Eustacchio, Angela %A Danesh, John %A Davies, Gail %A Bakker, Paul I W %A Groot, Mark C H %A Mutsert, Renée %A Deary, Ian J %A Dedoussis, George %A Demerath, Ellen W %A Heijer, Martin %A Hollander, Anneke I %A Ruijter, Hester M %A Dennis, Joe G %A Denny, Josh C %A Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dube, Marie-Pierre %A Dunning, Alison M %A Easton, Douglas F %A Edwards, Todd L %A Ellinghaus, David %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Farooqi, I Sadaf %A Faul, Jessica D %A Fauser, Sascha %A Feng, Shuang %A Ferrannini, Ele %A Ferrieres, Jean %A Florez, Jose C %A Ford, Ian %A Fornage, Myriam %A Franco, Oscar H %A Franke, Andre %A Franks, Paul W %A Friedrich, Nele %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Gibson, Jane %A Giedraitis, Vilmantas %A Gjesing, Anette P %A Gordon-Larsen, Penny %A Gorski, Mathias %A Grabe, Hans-Jörgen %A Grant, Struan F A %A Grarup, Niels %A Griffiths, Helen L %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Haessler, Jeff %A Hakonarson, Hakon %A Hammerschlag, Anke R %A Hansen, Torben %A Harris, Kathleen Mullan %A Harris, Tamara B %A Hattersley, Andrew T %A Have, Christian T %A Hayward, Caroline %A He, Liang %A Heard-Costa, Nancy L %A Heath, Andrew C %A Heid, Iris M %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hu, Yao %A Huang, Paul L %A Huffman, Jennifer E %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jia, Yucheng %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kathiresan, Sekar %A Kee, Frank %A Kiemeney, Lambertus A %A Kim, Eric %A Kitajima, Hidetoshi %A Komulainen, Pirjo %A Kooner, Jaspal S %A Kooperberg, Charles %A Korhonen, Tellervo %A Kovacs, Peter %A Kuivaniemi, Helena %A Kutalik, Zoltán %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Laakso, Markku %A Lakka, Timo A %A Lamparter, David %A Lange, Ethan M %A Lange, Leslie A %A Langenberg, Claudia %A Larson, Eric B %A Lee, Nanette R %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Keng-Hung %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Dajiang J %A Liu, Yongmei %A Lo, Ken S %A Lophatananon, Artitaya %A Lotery, Andrew J %A Loukola, Anu %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Männistö, Satu %A Marenne, Gaëlle %A Mazul, Angela L %A McCarthy, Mark I %A McKean-Cowdin, Roberta %A Medland, Sarah E %A Meidtner, Karina %A Milani, Lili %A Mistry, Vanisha %A Mitchell, Paul %A Mohlke, Karen L %A Moilanen, Leena %A Moitry, Marie %A Montgomery, Grant W %A Mook-Kanamori, Dennis O %A Moore, Carmel %A Mori, Trevor A %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Nalls, Mike A %A Narisu, Narisu %A Nelson, Christopher P %A Neville, Matt %A Nielsen, Sune F %A Nikus, Kjell %A Njølstad, Pål R %A Nordestgaard, Børge G %A Nyholt, Dale R %A O'Connel, Jeffrey R %A O'Donoghue, Michelle L %A Olde Loohuis, Loes M %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Palmer, Nicholette D %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Pers, Tune H %A Person, Thomas N %A Peters, Annette %A Petersen, Eva R B %A Peyser, Patricia A %A Pirie, Ailith %A Polasek, Ozren %A Polderman, Tinca J %A Puolijoki, Hannu %A Raitakari, Olli T %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Renstrom, Frida %A Rheinberger, Myriam %A Ridker, Paul M %A Rioux, John D %A Rivas, Manuel A %A Roberts, David J %A Robertson, Neil R %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Sapkota, Yadav %A Sattar, Naveed %A Schoen, Robert E %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Shah, Svati H %A Sheu, Wayne H-H %A Sim, Xueling %A Slater, Andrew J %A Small, Kerrin S %A Smith, Albert V %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Starr, John M %A Stefansson, Kari %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen E %A Strauch, Konstantin %A Stringham, Heather M %A Stumvoll, Michael %A Sun, Liang %A Surendran, Praveen %A Swift, Amy J %A Tada, Hayato %A Tansey, Katherine E %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorleifsson, Gudmar %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tonjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A Uitterlinden, André G %A Uusitupa, Matti %A Laan, Sander W %A Duijn, Cornelia M %A Leeuwen, Nienke %A van Setten, Jessica %A Vanhala, Mauno %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Velez Edwards, Digna R %A Vermeulen, Sita H %A Veronesi, Giovanni %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Völker, Uwe %A Vuckovic, Dragana %A Wagenknecht, Lynne E %A Walker, Mark %A Wallentin, Lars %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Ware, Erin B %A Wareham, Nicholas J %A Warren, Helen R %A Waterworth, Dawn M %A Wessel, Jennifer %A White, Harvey D %A Willer, Cristen J %A Wilson, James G %A Witte, Daniel R %A Wood, Andrew R %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zhou, Wei %A Zondervan, Krina T %A Rotter, Jerome I %A Pospisilik, John A %A Rivadeneira, Fernando %A Borecki, Ingrid B %A Deloukas, Panos %A Frayling, Timothy M %A Lettre, Guillaume %A North, Kari E %A Lindgren, Cecilia M %A Hirschhorn, Joel N %A Loos, Ruth J F %X

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

%B Nat Genet %V 50 %P 765-766 %8 2018 May %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/29549329?dopt=Abstract %R 10.1038/s41588-018-0050-y %0 Journal Article %J Nature %D 2017 %T Rare and low-frequency coding variants alter human adult height. %A Marouli, Eirini %A Graff, Mariaelisa %A Medina-Gomez, Carolina %A Lo, Ken Sin %A Wood, Andrew R %A Kjaer, Troels R %A Fine, Rebecca S %A Lu, Yingchang %A Schurmann, Claudia %A Highland, Heather M %A Rüeger, Sina %A Thorleifsson, Gudmar %A Justice, Anne E %A Lamparter, David %A Stirrups, Kathleen E %A Turcot, Valérie %A Young, Kristin L %A Winkler, Thomas W %A Esko, Tõnu %A Karaderi, Tugce %A Locke, Adam E %A Masca, Nicholas G D %A Ng, Maggie C Y %A Mudgal, Poorva %A Rivas, Manuel A %A Vedantam, Sailaja %A Mahajan, Anubha %A Guo, Xiuqing %A Abecasis, Goncalo %A Aben, Katja K %A Adair, Linda S %A Alam, Dewan S %A Albrecht, Eva %A Allin, Kristine H %A Allison, Matthew %A Amouyel, Philippe %A Appel, Emil V %A Arveiler, Dominique %A Asselbergs, Folkert W %A Auer, Paul L %A Balkau, Beverley %A Banas, Bernhard %A Bang, Lia E %A Benn, Marianne %A Bergmann, Sven %A Bielak, Lawrence F %A Blüher, Matthias %A Boeing, Heiner %A Eric Boerwinkle %A Böger, Carsten A %A Bonnycastle, Lori L %A Bork-Jensen, Jette %A Bots, Michiel L %A Bottinger, Erwin P %A Bowden, Donald W %A Brandslund, Ivan %A Breen, Gerome %A Brilliant, Murray H %A Broer, Linda %A Burt, Amber A %A Butterworth, Adam S %A Carey, David J %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Chen, Yii-Der Ida %A Chowdhury, Rajiv %A Christensen, Cramer %A Chu, Audrey Y %A Cocca, Massimiliano %A Collins, Francis S %A Cook, James P %A Corley, Janie %A Galbany, Jordi Corominas %A Cox, Amanda J %A Cuellar-Partida, Gabriel %A Danesh, John %A Davies, Gail %A de Bakker, Paul I W %A de Borst, Gert J %A de Denus, Simon %A de Groot, Mark C H %A de Mutsert, Renée %A Deary, Ian J %A Dedoussis, George %A Demerath, Ellen W %A den Hollander, Anneke I %A Dennis, Joe G %A Di Angelantonio, Emanuele %A Drenos, Fotios %A Du, Mengmeng %A Dunning, Alison M %A Easton, Douglas F %A Ebeling, Tapani %A Edwards, Todd L %A Ellinor, Patrick T %A Elliott, Paul %A Evangelou, Evangelos %A Farmaki, Aliki-Eleni %A Faul, Jessica D %A Feitosa, Mary F %A Feng, Shuang %A Ferrannini, Ele %A Ferrario, Marco M %A Ferrieres, Jean %A Florez, Jose C %A Ford, Ian %A Fornage, Myriam %A Franks, Paul W %A Frikke-Schmidt, Ruth %A Galesloot, Tessel E %A Gan, Wei %A Gandin, Ilaria %A Gasparini, Paolo %A Giedraitis, Vilmantas %A Giri, Ayush %A Girotto, Giorgia %A Gordon, Scott D %A Gordon-Larsen, Penny %A Gorski, Mathias %A Grarup, Niels %A Grove, Megan L %A Gudnason, Vilmundur %A Gustafsson, Stefan %A Hansen, Torben %A Harris, Kathleen Mullan %A Harris, Tamara B %A Hattersley, Andrew T %A Hayward, Caroline %A He, Liang %A Heid, Iris M %A Heikkilä, Kauko %A Helgeland, Øyvind %A Hernesniemi, Jussi %A Hewitt, Alex W %A Hocking, Lynne J %A Hollensted, Mette %A Holmen, Oddgeir L %A Hovingh, G Kees %A Howson, Joanna M M %A Hoyng, Carel B %A Huang, Paul L %A Hveem, Kristian %A Ikram, M Arfan %A Ingelsson, Erik %A Jackson, Anne U %A Jansson, Jan-Håkan %A Jarvik, Gail P %A Jensen, Gorm B %A Jhun, Min A %A Jia, Yucheng %A Jiang, Xuejuan %A Johansson, Stefan %A Jørgensen, Marit E %A Jørgensen, Torben %A Jousilahti, Pekka %A Jukema, J Wouter %A Kahali, Bratati %A Kahn, René S %A Kähönen, Mika %A Kamstrup, Pia R %A Kanoni, Stavroula %A Kaprio, Jaakko %A Karaleftheri, Maria %A Kardia, Sharon L R %A Karpe, Fredrik %A Kee, Frank %A Keeman, Renske %A Kiemeney, Lambertus A %A Kitajima, Hidetoshi %A Kluivers, Kirsten B %A Kocher, Thomas %A Komulainen, Pirjo %A Kontto, Jukka %A Kooner, Jaspal S %A Kooperberg, Charles %A Kovacs, Peter %A Kriebel, Jennifer %A Kuivaniemi, Helena %A Küry, Sébastien %A Kuusisto, Johanna %A La Bianca, Martina %A Laakso, Markku %A Lakka, Timo A %A Lange, Ethan M %A Lange, Leslie A %A Langefeld, Carl D %A Langenberg, Claudia %A Larson, Eric B %A Lee, I-Te %A Lehtimäki, Terho %A Lewis, Cora E %A Li, Huaixing %A Li, Jin %A Li-Gao, Ruifang %A Lin, Honghuang %A Lin, Li-An %A Lin, Xu %A Lind, Lars %A Lindström, Jaana %A Linneberg, Allan %A Liu, Yeheng %A Liu, Yongmei %A Lophatananon, Artitaya %A Luan, Jian'an %A Lubitz, Steven A %A Lyytikäinen, Leo-Pekka %A Mackey, David A %A Madden, Pamela A F %A Manning, Alisa K %A Männistö, Satu %A Marenne, Gaëlle %A Marten, Jonathan %A Martin, Nicholas G %A Mazul, Angela L %A Meidtner, Karina %A Metspalu, Andres %A Mitchell, Paul %A Mohlke, Karen L %A Mook-Kanamori, Dennis O %A Morgan, Anna %A Morris, Andrew D %A Morris, Andrew P %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Nalls, Mike A %A Nauck, Matthias %A Nelson, Christopher P %A Neville, Matt %A Nielsen, Sune F %A Nikus, Kjell %A Njølstad, Pål R %A Nordestgaard, Børge G %A Ntalla, Ioanna %A O'Connel, Jeffrey R %A Oksa, Heikki %A Loohuis, Loes M Olde %A Ophoff, Roel A %A Owen, Katharine R %A Packard, Chris J %A Padmanabhan, Sandosh %A Palmer, Colin N A %A Pasterkamp, Gerard %A Patel, Aniruddh P %A Pattie, Alison %A Pedersen, Oluf %A Peissig, Peggy L %A Peloso, Gina M %A Pennell, Craig E %A Perola, Markus %A Perry, James A %A Perry, John R B %A Person, Thomas N %A Pirie, Ailith %A Polasek, Ozren %A Posthuma, Danielle %A Raitakari, Olli T %A Rasheed, Asif %A Rauramaa, Rainer %A Reilly, Dermot F %A Reiner, Alex P %A Renstrom, Frida %A Ridker, Paul M %A Rioux, John D %A Robertson, Neil %A Robino, Antonietta %A Rolandsson, Olov %A Rudan, Igor %A Ruth, Katherine S %A Saleheen, Danish %A Salomaa, Veikko %A Samani, Nilesh J %A Sandow, Kevin %A Sapkota, Yadav %A Sattar, Naveed %A Schmidt, Marjanka K %A Schreiner, Pamela J %A Schulze, Matthias B %A Scott, Robert A %A Segura-Lepe, Marcelo P %A Shah, Svati %A Sim, Xueling %A Sivapalaratnam, Suthesh %A Small, Kerrin S %A Smith, Albert Vernon %A Smith, Jennifer A %A Southam, Lorraine %A Spector, Timothy D %A Speliotes, Elizabeth K %A Starr, John M %A Steinthorsdottir, Valgerdur %A Stringham, Heather M %A Stumvoll, Michael %A Surendran, Praveen %A 't Hart, Leen M %A Tansey, Katherine E %A Tardif, Jean-Claude %A Taylor, Kent D %A Teumer, Alexander %A Thompson, Deborah J %A Thorsteinsdottir, Unnur %A Thuesen, Betina H %A Tonjes, Anke %A Tromp, Gerard %A Trompet, Stella %A Tsafantakis, Emmanouil %A Tuomilehto, Jaakko %A Tybjaerg-Hansen, Anne %A Tyrer, Jonathan P %A Uher, Rudolf %A Uitterlinden, André G %A Ulivi, Sheila %A van der Laan, Sander W %A Van Der Leij, Andries R %A van Duijn, Cornelia M %A van Schoor, Natasja M %A van Setten, Jessica %A Varbo, Anette %A Varga, Tibor V %A Varma, Rohit %A Edwards, Digna R Velez %A Vermeulen, Sita H %A Vestergaard, Henrik %A Vitart, Veronique %A Vogt, Thomas F %A Vozzi, Diego %A Walker, Mark %A Wang, Feijie %A Wang, Carol A %A Wang, Shuai %A Wang, Yiqin %A Wareham, Nicholas J %A Warren, Helen R %A Wessel, Jennifer %A Willems, Sara M %A Wilson, James G %A Witte, Daniel R %A Woods, Michael O %A Wu, Ying %A Yaghootkar, Hanieh %A Yao, Jie %A Yao, Pang %A Yerges-Armstrong, Laura M %A Young, Robin %A Zeggini, Eleftheria %A Zhan, Xiaowei %A Zhang, Weihua %A Zhao, Jing Hua %A Zhao, Wei %A Zhao, Wei %A Zheng, He %A Zhou, Wei %A Rotter, Jerome I %A Boehnke, Michael %A Kathiresan, Sekar %A McCarthy, Mark I %A Willer, Cristen J %A Stefansson, Kari %A Borecki, Ingrid B %A Liu, Dajiang J %A North, Kari E %A Heard-Costa, Nancy L %A Pers, Tune H %A Lindgren, Cecilia M %A Oxvig, Claus %A Kutalik, Zoltán %A Rivadeneira, Fernando %A Loos, Ruth J F %A Frayling, Timothy M %A Hirschhorn, Joel N %A Deloukas, Panos %A Lettre, Guillaume %K ADAMTS Proteins %K Adult %K Alleles %K Body Height %K Cell Adhesion Molecules %K Female %K Gene Frequency %K Genetic Variation %K Genome, Human %K Glycoproteins %K Glycosaminoglycans %K Hedgehog Proteins %K Humans %K Intercellular Signaling Peptides and Proteins %K Interferon Regulatory Factors %K Interleukin-11 Receptor alpha Subunit %K Male %K Multifactorial Inheritance %K NADPH Oxidase 4 %K NADPH Oxidases %K Phenotype %K Pregnancy-Associated Plasma Protein-A %K Procollagen N-Endopeptidase %K Proteoglycans %K Proteolysis %K Receptors, Androgen %K Somatomedins %X

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

%B Nature %V 542 %P 186-190 %8 2017 Feb 09 %G eng %N 7640 %1 https://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract %R 10.1038/nature21039 %0 Journal Article %J Sci Transl Med %D 2016 %T A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. %A Scott, Robert A %A Freitag, Daniel F %A Li, Li %A Chu, Audrey Y %A Surendran, Praveen %A Young, Robin %A Grarup, Niels %A Stančáková, Alena %A Chen, Yuning %A Varga, Tibor V %A Yaghootkar, Hanieh %A Luan, Jian'an %A Zhao, Jing Hua %A Willems, Sara M %A Wessel, Jennifer %A Wang, Shuai %A Maruthur, Nisa %A Michailidou, Kyriaki %A Pirie, Ailith %A van der Lee, Sven J %A Gillson, Christopher %A Al Olama, Ali Amin %A Amouyel, Philippe %A Arriola, Larraitz %A Arveiler, Dominique %A Aviles-Olmos, Iciar %A Balkau, Beverley %A Barricarte, Aurelio %A Barroso, Inês %A Garcia, Sara Benlloch %A Bis, Joshua C %A Blankenberg, Stefan %A Boehnke, Michael %A Boeing, Heiner %A Eric Boerwinkle %A Borecki, Ingrid B %A Bork-Jensen, Jette %A Bowden, Sarah %A Caldas, Carlos %A Caslake, Muriel %A Cupples, L Adrienne %A Cruchaga, Carlos %A Czajkowski, Jacek %A den Hoed, Marcel %A Dunn, Janet A %A Earl, Helena M %A Ehret, Georg B %A Ferrannini, Ele %A Ferrieres, Jean %A Foltynie, Thomas %A Ford, Ian %A Forouhi, Nita G %A Gianfagna, Francesco %A Gonzalez, Carlos %A Grioni, Sara %A Hiller, Louise %A Jansson, Jan-Håkan %A Jørgensen, Marit E %A Jukema, J Wouter %A Kaaks, Rudolf %A Kee, Frank %A Kerrison, Nicola D %A Key, Timothy J %A Kontto, Jukka %A Kote-Jarai, Zsofia %A Kraja, Aldi T %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Linneberg, Allan %A Liu, Chunyu %A Marenne, Gaëlle %A Mohlke, Karen L %A Morris, Andrew P %A Muir, Kenneth %A Müller-Nurasyid, Martina %A Munroe, Patricia B %A Navarro, Carmen %A Nielsen, Sune F %A Nilsson, Peter M %A Nordestgaard, Børge G %A Packard, Chris J %A Palli, Domenico %A Panico, Salvatore %A Peloso, Gina M %A Perola, Markus %A Peters, Annette %A Poole, Christopher J %A Quirós, J Ramón %A Rolandsson, Olov %A Sacerdote, Carlotta %A Salomaa, Veikko %A Sánchez, María-José %A Sattar, Naveed %A Sharp, Stephen J %A Sims, Rebecca %A Slimani, Nadia %A Smith, Jennifer A %A Thompson, Deborah J %A Trompet, Stella %A Tumino, Rosario %A van der A, Daphne L %A van der Schouw, Yvonne T %A Virtamo, Jarmo %A Walker, Mark %A Walter, Klaudia %A Abraham, Jean E %A Amundadottir, Laufey T %A Aponte, Jennifer L %A Butterworth, Adam S %A Dupuis, Josée %A Easton, Douglas F %A Eeles, Rosalind A %A Erdmann, Jeanette %A Franks, Paul W %A Frayling, Timothy M %A Hansen, Torben %A Howson, Joanna M M %A Jørgensen, Torben %A Kooner, Jaspal %A Laakso, Markku %A Langenberg, Claudia %A McCarthy, Mark I %A Pankow, James S %A Pedersen, Oluf %A Riboli, Elio %A Rotter, Jerome I %A Saleheen, Danish %A Samani, Nilesh J %A Schunkert, Heribert %A Vollenweider, Peter %A O'Rahilly, Stephen %A Deloukas, Panos %A Danesh, John %A Goodarzi, Mark O %A Kathiresan, Sekar %A Meigs, James B %A Ehm, Margaret G %A Wareham, Nicholas J %A Waterworth, Dawn M %K Alleles %K Coronary Disease %K Diabetes Mellitus, Type 2 %K Dipeptidyl Peptidase 4 %K Genotype %K Glucagon-Like Peptide-1 Receptor %K Humans %K Obesity %K Receptor, Cannabinoid, CB2 %K Receptor, Serotonin, 5-HT2C %K Receptors, Somatostatin %K Sodium-Glucose Transporter 1 %X

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

%B Sci Transl Med %V 8 %P 341ra76 %8 2016 Jun 01 %G eng %N 341 %1 https://www.ncbi.nlm.nih.gov/pubmed/27252175?dopt=Abstract %R 10.1126/scitranslmed.aad3744 %0 Journal Article %J Nat Commun %D 2015 %T Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. %A Wessel, Jennifer %A Chu, Audrey Y %A Willems, Sara M %A Wang, Shuai %A Yaghootkar, Hanieh %A Brody, Jennifer A %A Dauriz, Marco %A Hivert, Marie-France %A Raghavan, Sridharan %A Lipovich, Leonard %A Hidalgo, Bertha %A Fox, Keolu %A Huffman, Jennifer E %A An, Ping %A Lu, Yingchang %A Rasmussen-Torvik, Laura J %A Grarup, Niels %A Ehm, Margaret G %A Li, Li %A Baldridge, Abigail S %A Stančáková, Alena %A Abrol, Ravinder %A Besse, Céline %A Boland, Anne %A Bork-Jensen, Jette %A Fornage, Myriam %A Freitag, Daniel F %A Garcia, Melissa E %A Guo, Xiuqing %A Hara, Kazuo %A Isaacs, Aaron %A Jakobsdottir, Johanna %A Lange, Leslie A %A Layton, Jill C %A Li, Man %A Hua Zhao, Jing %A Meidtner, Karina %A Morrison, Alanna C %A Nalls, Mike A %A Peters, Marjolein J %A Sabater-Lleal, Maria %A Schurmann, Claudia %A Silveira, Angela %A Smith, Albert V %A Southam, Lorraine %A Stoiber, Marcus H %A Strawbridge, Rona J %A Taylor, Kent D %A Varga, Tibor V %A Allin, Kristine H %A Amin, Najaf %A Aponte, Jennifer L %A Aung, Tin %A Barbieri, Caterina %A Bihlmeyer, Nathan A %A Boehnke, Michael %A Bombieri, Cristina %A Bowden, Donald W %A Burns, Sean M %A Chen, Yuning %A Chen, Yii-DerI %A Cheng, Ching-Yu %A Correa, Adolfo %A Czajkowski, Jacek %A Dehghan, Abbas %A Ehret, Georg B %A Eiriksdottir, Gudny %A Escher, Stefan A %A Farmaki, Aliki-Eleni %A Frånberg, Mattias %A Gambaro, Giovanni %A Giulianini, Franco %A Goddard, William A %A Goel, Anuj %A Gottesman, Omri %A Grove, Megan L %A Gustafsson, Stefan %A Hai, Yang %A Hallmans, Goran %A Heo, Jiyoung %A Hoffmann, Per %A Ikram, Mohammad K %A Jensen, Richard A %A Jørgensen, Marit E %A Jørgensen, Torben %A Karaleftheri, Maria %A Khor, Chiea C %A Kirkpatrick, Andrea %A Kraja, Aldi T %A Kuusisto, Johanna %A Lange, Ethan M %A Lee, I T %A Lee, Wen-Jane %A Leong, Aaron %A Liao, Jiemin %A Liu, Chunyu %A Liu, Yongmei %A Lindgren, Cecilia M %A Linneberg, Allan %A Malerba, Giovanni %A Mamakou, Vasiliki %A Marouli, Eirini %A Maruthur, Nisa M %A Matchan, Angela %A McKean-Cowdin, Roberta %A McLeod, Olga %A Metcalf, Ginger A %A Mohlke, Karen L %A Muzny, Donna M %A Ntalla, Ioanna %A Palmer, Nicholette D %A Pasko, Dorota %A Peter, Andreas %A Rayner, Nigel W %A Renstrom, Frida %A Rice, Ken %A Sala, Cinzia F %A Sennblad, Bengt %A Serafetinidis, Ioannis %A Smith, Jennifer A %A Soranzo, Nicole %A Speliotes, Elizabeth K %A Stahl, Eli A %A Stirrups, Kathleen %A Tentolouris, Nikos %A Thanopoulou, Anastasia %A Torres, Mina %A Traglia, Michela %A Tsafantakis, Emmanouil %A Javad, Sundas %A Yanek, Lisa R %A Zengini, Eleni %A Becker, Diane M %A Bis, Joshua C %A Brown, James B %A Cupples, L Adrienne %A Hansen, Torben %A Ingelsson, Erik %A Karter, Andrew J %A Lorenzo, Carlos %A Mathias, Rasika A %A Norris, Jill M %A Peloso, Gina M %A Sheu, Wayne H-H %A Toniolo, Daniela %A Vaidya, Dhananjay %A Varma, Rohit %A Wagenknecht, Lynne E %A Boeing, Heiner %A Bottinger, Erwin P %A Dedoussis, George %A Deloukas, Panos %A Ferrannini, Ele %A Franco, Oscar H %A Franks, Paul W %A Gibbs, Richard A %A Gudnason, Vilmundur %A Hamsten, Anders %A Harris, Tamara B %A Hattersley, Andrew T %A Hayward, Caroline %A Hofman, Albert %A Jansson, Jan-Håkan %A Langenberg, Claudia %A Launer, Lenore J %A Levy, Daniel %A Oostra, Ben A %A O'Donnell, Christopher J %A O'Rahilly, Stephen %A Padmanabhan, Sandosh %A Pankow, James S %A Polasek, Ozren %A Province, Michael A %A Rich, Stephen S %A Ridker, Paul M %A Rudan, Igor %A Schulze, Matthias B %A Smith, Blair H %A Uitterlinden, André G %A Walker, Mark %A Watkins, Hugh %A Wong, Tien Y %A Zeggini, Eleftheria %A Laakso, Markku %A Borecki, Ingrid B %A Chasman, Daniel I %A Pedersen, Oluf %A Psaty, Bruce M %A Tai, E Shyong %A van Duijn, Cornelia M %A Wareham, Nicholas J %A Waterworth, Dawn M %A Boerwinkle, Eric %A Kao, W H Linda %A Florez, Jose C %A Loos, Ruth J F %A Wilson, James G %A Frayling, Timothy M %A Siscovick, David S %A Dupuis, Josée %A Rotter, Jerome I %A Meigs, James B %A Scott, Robert A %A Goodarzi, Mark O %K Black People %K Blood Glucose %K Diabetes Mellitus, Type 2 %K Exome %K Fasting %K Genetic Association Studies %K Genetic Loci %K Genetic Predisposition to Disease %K Genetic Variation %K Glucagon-Like Peptide-1 Receptor %K Glucose-6-Phosphatase %K Humans %K Insulin %K Mutation Rate %K Oligonucleotide Array Sequence Analysis %K Polymorphism, Single Nucleotide %K White People %X

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

%B Nat Commun %V 6 %P 5897 %8 2015 Jan 29 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/25631608?dopt=Abstract %R 10.1038/ncomms6897