Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

TitleProtein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.
Publication TypeJournal Article
Year of Publication2019
AuthorsJustice, AE, Karaderi, T, Highland, HM, Young, KL, Graff, M, Lu, Y, Turcot, V, Auer, PL, Fine, RS, Guo, X, Schurmann, C, Lempradl, A, Marouli, E, Mahajan, A, Winkler, TW, Locke, AE, Medina-Gomez, C, Esko, T, Vedantam, S, Giri, A, Lo, KSin, Alfred, T, Mudgal, P, C Y Ng, M, Heard-Costa, NL, Feitosa, MF, Manning, AK, Willems, SM, Sivapalaratnam, S, Abecasis, G, Alam, DS, Allison, M, Amouyel, P, Arzumanyan, Z, Balkau, B, Bastarache, L, Bergmann, S, Bielak, LF, Blüher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Böger, CA, Bork-Jensen, J, Bottinger, EP, Bowden, DW, Brandslund, I, Broer, L, Burt, AA, Butterworth, AS, Caulfield, MJ, Cesana, G, Chambers, JC, Chasman, DI, Chen, Y-DIda, Chowdhury, iv, R, Christensen, C, Chu, AY, Collins, FS, Cook, JP, Cox, AJ, Crosslin, DS, Danesh, J, de Bakker, PIW, de Denus, S, de Mutsert, R, Dedoussis, G, Demerath, EW, Dennis, JG, Denny, JC, Di Angelantonio, E, Dörr, M, Drenos, F, Dube, M-P, Dunning, AM, Easton, DF, Elliott, P, Evangelou, E, Farmaki, A-E, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Fornage, M, Fox, CS, Franks, PW, Friedrich, N, Gan, W, Gandin, I, Gasparini, P, Giedraitis, V, Girotto, G, Gorski, M, Grallert, H, Grarup, N, Grove, ML, Gustafsson, S, Haessler, J, Hansen, T, Hattersley, AT, Hayward, C, Heid, IM, Holmen, OL, G Hovingh, K, Howson, JMM, Hu, Y, Hung, Y-J, Hveem, K, M Ikram, A, Ingelsson, E, Jackson, AU, Jarvik, GP, Jia, Y, Jørgensen, T, Jousilahti, P, Justesen, JM, Kahali, B, Karaleftheri, M, Kardia, SLR, Karpe, F, Kee, F, Kitajima, H, Komulainen, P, Kooner, JS, Kovacs, P, Krämer, BK, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lee, W-J, Lehtimäki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, L-A, Lin, X, Lind, L, Lindström, J, Linneberg, A, Liu, C-T, Liu, DJ, Luan, J'an, Lyytikäinen, L-P, MacGregor, S, Mägi, R, Männistö, S, Marenne, G, Marten, J, Masca, NGD, McCarthy, MI, Meidtner, K, Mihailov, E, Moilanen, L, Moitry, M, Mook-Kanamori, DO, Morgan, A, Morris, AP, Müller-Nurasyid, M, Munroe, PB, Narisu, N, Nelson, CP, Neville, M, Ntalla, I, O'Connell, JR, Owen, KR, Pedersen, O, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Ewing, A, Polasek, O, Raitakari, OT, Rasheed, A, Raulerson, CK, Rauramaa, R, Reilly, DF, Reiner, AP, Ridker, PM, Rivas, MA, Robertson, NR, Robino, A, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, M, Sim, X, Slater, AJ, Small, KS, Smith, BH, Smith, JA, Southam, L, Spector, TD, Speliotes, EK, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swart, KMA, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Torres, M, Tsafantakis, E, Tuomilehto, J, Uitterlinden, AG, Uusitupa, M, van Duijn, CM, Vanhala, M, Varma, R, Vermeulen, SH, Vestergaard, H, Vitart, V, Vogt, TF, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JHua, Zhao, W, Zheng, H, Zhou, W, M Zillikens, C, Rivadeneira, F, Borecki, IB, J Pospisilik, A, Deloukas, P, Frayling, TM, Lettre, G, Mohlke, KL, Rotter, JI, Kutalik, Z, Hirschhorn, JN, L Cupples, A, Loos, RJF, North, KE, Lindgren, CM
Corporate AuthorsCHD Exome+ Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, InterAct, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators
JournalNat Genet
Volume51
Issue3
Pagination452-469
Date Published2019 03
ISSN1546-1718
KeywordsAnimals, Body Fat Distribution, Body Mass Index, Case-Control Studies, Drosophila, Exome, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Homeostasis, Humans, Lipids, Male, Proteins, Risk Factors, Waist-Hip Ratio
Abstract

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

DOI10.1038/s41588-018-0334-2
Alternate JournalNat. Genet.
PubMed ID30778226
Grant ListK12 HD043483 / HD / NICHD NIH HHS / United States
R01 DK106621 / DK / NIDDK NIH HHS / United States
RG/14/5/30893 / / British Heart Foundation / United Kingdom
T32 HL007055 / HL / NHLBI NIH HHS / United States