%0 Journal Article %J Nat Commun %D 2018 %T GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. %A Franceschini, Nora %A Giambartolomei, Claudia %A de Vries, Paul S %A Finan, Chris %A Bis, Joshua C %A Huntley, Rachael P %A Lovering, Ruth C %A Tajuddin, Salman M %A Winkler, Thomas W %A Graff, Misa %A Kavousi, Maryam %A Dale, Caroline %A Smith, Albert V %A Hofer, Edith %A van Leeuwen, Elisabeth M %A Nolte, Ilja M %A Lu, Lingyi %A Scholz, Markus %A Sargurupremraj, Muralidharan %A Pitkänen, Niina %A Franzén, Oscar %A Joshi, Peter K %A Noordam, Raymond %A Marioni, Riccardo E %A Hwang, Shih-Jen %A Musani, Solomon K %A Schminke, Ulf %A Palmas, Walter %A Isaacs, Aaron %A Correa, Adolfo %A Zonderman, Alan B %A Hofman, Albert %A Teumer, Alexander %A Cox, Amanda J %A Uitterlinden, André G %A Wong, Andrew %A Smit, Andries J %A Newman, Anne B %A Britton, Annie %A Ruusalepp, Arno %A Sennblad, Bengt %A Hedblad, Bo %A Pasaniuc, Bogdan %A Penninx, Brenda W %A Langefeld, Carl D %A Wassel, Christina L %A Tzourio, Christophe %A Fava, Cristiano %A Baldassarre, Damiano %A O'Leary, Daniel H %A Teupser, Daniel %A Kuh, Diana %A Tremoli, Elena %A Mannarino, Elmo %A Grossi, Enzo %A Eric Boerwinkle %A Schadt, Eric E %A Ingelsson, Erik %A Veglia, Fabrizio %A Rivadeneira, Fernando %A Beutner, Frank %A Chauhan, Ganesh %A Heiss, Gerardo %A Snieder, Harold %A Campbell, Harry %A Völzke, Henry %A Markus, Hugh S %A Deary, Ian J %A Jukema, J Wouter %A de Graaf, Jacqueline %A Price, Jacqueline %A Pott, Janne %A Hopewell, Jemma C %A Liang, Jingjing %A Thiery, Joachim %A Engmann, Jorgen %A Gertow, Karl %A Rice, Kenneth %A Taylor, Kent D %A Dhana, Klodian %A Kiemeney, Lambertus A L M %A Lind, Lars %A Raffield, Laura M %A Launer, Lenore J %A Holdt, Lesca M %A Dörr, Marcus %A Dichgans, Martin %A Traylor, Matthew %A Sitzer, Matthias %A Kumari, Meena %A Kivimaki, Mika %A Nalls, Mike A %A Melander, Olle %A Raitakari, Olli %A Franco, Oscar H %A Rueda-Ochoa, Oscar L %A Roussos, Panos %A Whincup, Peter H %A Amouyel, Philippe %A Giral, Philippe %A Anugu, Pramod %A Wong, Quenna %A Malik, Rainer %A Rauramaa, Rainer %A Burkhardt, Ralph %A Hardy, Rebecca %A Schmidt, Reinhold %A de Mutsert, Renée %A Morris, Richard W %A Strawbridge, Rona J %A Wannamethee, S Goya %A Hägg, Sara %A Shah, Sonia %A McLachlan, Stela %A Trompet, Stella %A Seshadri, Sudha %A Kurl, Sudhir %A Heckbert, Susan R %A Ring, Susan %A Harris, Tamara B %A Lehtimäki, Terho %A Galesloot, Tessel E %A Shah, Tina %A de Faire, Ulf %A Plagnol, Vincent %A Rosamond, Wayne D %A Post, Wendy %A Zhu, Xiaofeng %A Zhang, Xiaoling %A Guo, Xiuqing %A Saba, Yasaman %A Dehghan, Abbas %A Seldenrijk, Adrie %A Morrison, Alanna C %A Hamsten, Anders %A Psaty, Bruce M %A van Duijn, Cornelia M %A Lawlor, Deborah A %A Mook-Kanamori, Dennis O %A Bowden, Donald W %A Schmidt, Helena %A Wilson, James F %A Wilson, James G %A Rotter, Jerome I %A Wardlaw, Joanna M %A Deanfield, John %A Halcox, Julian %A Lyytikäinen, Leo-Pekka %A Loeffler, Markus %A Evans, Michele K %A Debette, Stephanie %A Humphries, Steve E %A Völker, Uwe %A Gudnason, Vilmundur %A Hingorani, Aroon D %A Björkegren, Johan L M %A Casas, Juan P %A O'Donnell, Christopher J %K ADAMTS9 Protein %K Amino Acid Oxidoreductases %K Carotid Intima-Media Thickness %K Coronary Disease %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Humans %K Lod Score %K Plaque, Atherosclerotic %K Polymorphism, Single Nucleotide %K Protein-Lysine 6-Oxidase %K Quantitative Trait Loci %K Risk Factors %X

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

%B Nat Commun %V 9 %P 5141 %8 2018 Dec 03 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/30510157?dopt=Abstract %R 10.1038/s41467-018-07340-5 %0 Journal Article %J Nature %D 2006 %T The finished DNA sequence of human chromosome 12. %A Scherer, Steven E %A Donna M Muzny %A Buhay, Christian J %A Rui Chen %A Cree, Andrew %A Ding, Yan %A Dugan-Rocha, Shannon %A Gill, Rachel %A Gunaratne, Preethi %A R. Alan Harris %A Hawes, Alicia C %A Hernandez, Judith %A Hodgson, Anne V %A Hume, Jennifer %A Jackson, Andrew %A Ziad Khan %A Kovar-Smith, Christie %A Lewis, Lora R %A Lozado, Ryan J %A Metzker, Michael L %A Milosavljevic, Aleksandar %A Miner, George R %A Montgomery, Kate T %A Morgan, Margaret B %A Nazareth, Lynne V %A Scott, Graham %A Sodergren, Erica %A Song, Xing-Zhi %A Steffen, David %A Lovering, Ruth C %A Wheeler, David A %A Worley, Kim C %A Yuan, Yi %A Zhang, Zhengdong %A Adams, Charles Q %A Ansari-Lari, M Ali %A Ayele, Mulu %A Brown, Mary J %A Chen, Guan %A Chen, Zhijian %A Clerc-Blankenburg, Kerstin P %A Davis, Clay %A Delgado, Oliver %A Dinh, Huyen H %A Draper, Heather %A Gonzalez-Garay, Manuel L %A Havlak, Paul %A Jackson, Laronda R %A Jacob, Leni S %A Kelly, Susan H %A Li, Li %A Li, Zhangwan %A Liu, Jing %A Liu, Wen %A Lu, Jing %A Maheshwari, Manjula %A Nguyen, Bao-Viet %A Okwuonu, Geoffrey O %A Pasternak, Shiran %A Perez, Lesette M %A Plopper, Farah J H %A Santibanez, Jireh %A Shen, Hua %A Tabor, Paul E %A Verduzco, Daniel %A Waldron, Lenée %A Wang, Qiaoyan %A Williams, Gabrielle A %A Zhang, Jingkun %A Zhou, Jianling %A Allen, Carlana C %A Amin, Anita G %A Anyalebechi, Vivian %A Bailey, Michael %A Barbaria, Joseph A %A Bimage, Kesha E %A Bryant, Nathaniel P %A Burch, Paula E %A Burkett, Carrie E %A Burrell, Kevin L %A Calderon, Eliana %A Cardenas, Veronica %A Carter, Kelvin %A Casias, Kristal %A Cavazos, Iracema %A Cavazos, Sandra R %A Ceasar, Heather %A Chacko, Joseph %A Chan, Sheryl N %A Chavez, Dean %A Christopoulos, Constantine %A Chu, Joseph %A Cockrell, Raynard %A Cox, Caroline D %A Dang, Michelle %A Dathorne, Stephanie R %A David, Robert %A Davis, Candi Mon'Et %A Davy-Carroll, Latarsha %A Deshazo, Denise R %A Donlin, Jeremy E %A D'Souza, Lisa %A Eaves, Kristy A %A Simons, Rain %A Emery-Cohen, Alexandra J %A Escotto, Michael %A Flagg, Nicole %A Forbes, Lisa D %A Gabisi, Abdul M %A Garza, Melissa %A Hamilton, Cerissa %A Henderson, Nicholas %A Hernandez, Omar %A Hines, Sandra %A Hogues, Marilyn E %A Huang, Mei %A Idlebird, DeVincent G %A Johnson, Rudy %A Jolivet, Angela %A Jones, Sally %A Kagan, Ryan %A King, Laquisha M %A Leal, Belita %A Lebow, Heather %A Lee, Sandra %A LeVan, Jaclyn M %A Lewis, Lakeshia C %A London, Pamela %A Lorensuhewa, Lorna M %A Loulseged, Hermela %A Lovett, Demetria A %A Lucier, Alice %A Lucier, Raymond L %A Ma, Jie %A Madu, Renita C %A Mapua, Patricia %A Martindale, Ashley D %A Martinez, Evangelina %A Massey, Elizabeth %A Mawhiney, Samantha %A Meador, Michael G %A Mendez, Sylvia %A Mercado, Christian %A Mercado, Iracema C %A Merritt, Christina E %A Miner, Zachary L %A Minja, Emmanuel %A Mitchell, Teresa %A Mohabbat, Farida %A Mohabbat, Khatera %A Montgomery, Baize %A Moore, Niki %A Morris, Sidney %A Munidasa, Mala %A Ngo, Robin N %A Nguyen, Ngoc B %A Nickerson, Elizabeth %A Nwaokelemeh, Ogechi O %A Nwokenkwo, Stanley %A Obregon, Melissa %A Oguh, Maryann %A Oragunye, Njideka %A Oviedo, Rodolfo J %A Parish, Bridgette J %A Parker, David N %A Parrish, Julia %A Parks, Kenya L %A Paul, Heidie A %A Payton, Brett A %A Perez, Agapito %A Perrin, William %A Pickens, Adam %A Primus, Eltrick L %A Pu, Ling-Ling %A Puazo, Maria %A Quiles, Miyo M %A Quiroz, Juana B %A Rabata, Dina %A Reeves, Kacy %A Ruiz, San Juana %A Shao, Hongmei %A Sisson, Ida %A Sonaike, Titilola %A Sorelle, Richard P %A Sutton, Angelica E %A Svatek, Amanda F %A Svetz, Leah Anne %A Tamerisa, Kavitha S %A Taylor, Tineace R %A Teague, Brian %A Thomas, Nicole %A Thorn, Rachel D %A Trejos, Zulma Y %A Trevino, Brenda K %A Ukegbu, Ogechi N %A Urban, Jeremy B %A Vasquez, Lydia I %A Vera, Virginia A %A Villasana, Donna M %A Wang, Ling %A Ward-Moore, Stephanie %A Warren, James T %A Wei, Xuehong %A White, Flower %A Williamson, Angela L %A Wleczyk, Regina %A Wooden, Hailey S %A Wooden, Steven H %A Yen, Jennifer %A Yoon, Lillienne %A Yoon, Vivienne %A Zorrilla, Sara E %A Nelson, David %A Kucherlapati, Raju %A Weinstock, George %A Richard A Gibbs %K Animals %K Base Composition %K Chromosomes, Human, Pair 12 %K CpG Islands %K Evolution, Molecular %K Expressed Sequence Tags %K Genes %K Humans %K Linkage Disequilibrium %K Microsatellite Repeats %K Molecular Sequence Data %K Mutagenesis, Insertional %K Pan troglodytes %K Sequence Analysis, DNA %K Sequence Deletion %K Short Interspersed Nucleotide Elements %K Synteny %X

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.

%B Nature %V 440 %P 346-51 %8 2006 Mar 16 %G eng %N 7082 %1 https://www.ncbi.nlm.nih.gov/pubmed/16541075?dopt=Abstract %R 10.1038/nature04569