Title | Discovery and refinement of loci associated with lipid levels. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Willer, CJ, Schmidt, EM, Sengupta, S, Peloso, GM, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, ML, Mora, S, Beckmann, JS, Bragg-Gresham, JL, Chang, H-Y, Demirkan, A, Hertog, HMDen, Do, R, Donnelly, LA, Ehret, GB, Esko, T, Feitosa, MF, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, RM, Freitag, DF, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, AU, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, ME, Li, X, Luan, J'an, Lyytikäinen, L-P, Magnusson, PKE, Mangino, M, Mihailov, E, Montasser, ME, Müller-Nurasyid, M, Nolte, IM, O'Connell, JR, Palmer, CD, Perola, M, Petersen, A-K, Sanna, S, Saxena, R, Service, SK, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, RJ, Surakka, I, Tanaka, T, Teslovich, TM, Thorleifsson, G, van den Herik, EG, Voight, BF, Volcik, KA, Waite, LL, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, LF, Bolton, JL, Bonnycastle, LL, Brambilla, P, Burnett, MS, Cesana, G, Dimitriou, M, Doney, ASF, Döring, A, Elliott, P, Epstein, SE, Eyjolfsson, GIngi, Gigante, B, Goodarzi, MO, Grallert, H, Gravito, ML, Groves, CJ, Hallmans, G, Hartikainen, A-L, Hayward, C, Hernandez, D, Hicks, AA, Holm, H, Hung, Y-J, Illig, T, Jones, MR, Kaleebu, P, Kastelein, JJP, Khaw, K-T, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S-Y, Lindström, J, Loos, RJF, Mach, F, McArdle, WL, Meisinger, C, Mitchell, BD, Müller, G, Nagaraja, R, Narisu, N, Nieminen, TVM, Nsubuga, RN, Olafsson, I, Ong, KK, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, DJ, Reilly, MP, Ridker, PM, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stančáková, A, Stirrups, K, Swift, AJ, Tiret, L, Uitterlinden, AG, L van Pelt, J, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, SH, Willemsen, G, Wilsgaard, T, Wilson, JF, Young, EH, Zhao, JH, Adair, LS, Arveiler, D, Assimes, TL, Bandinelli, S, Bennett, F, Bochud, M, Boehm, BO, Boomsma, DI, Borecki, IB, Bornstein, SR, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, JC, Chen, Y-DI, Collins, FS, Cooper, RS, Danesh, J, Dedoussis, G, de Faire, U, Feranil, AB, Ferrieres, J, Ferrucci, L, Freimer, NB, Gieger, C, Groop, LC, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, TB, Hingorani, A, Hirschhorn, JN, Hofman, A, G Hovingh, K, Hsiung, CAgnes, Humphries, SE, Hunt, SC, Hveem, K, Iribarren, C, Jarvelin, M-R, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, JS, Koudstaal, PJ, Krauss, RM, Kuh, D, Kuusisto, J, Kyvik, KO, Laakso, M, Lakka, TA, Lind, L, Lindgren, CM, Martin, NG, März, W, McCarthy, MI, McKenzie, CA, Meneton, P, Metspalu, A, Moilanen, L, Morris, AD, Munroe, PB, Njølstad, I, Pedersen, NL, Power, C, Pramstaller, PP, Price, JF, Psaty, BM, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, DK, Saramies, J, Schwarz, PEH, Sheu, WH-H, Shuldiner, AR, Siegbahn, A, Spector, TD, Stefansson, K, Strachan, DP, Tayo, BO, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, CM, Vollenweider, P, Wallentin, L, Wareham, NJ, Whitfield, JB, Wolffenbuttel, BHR, Ordovas, JM, Boerwinkle, E, Palmer, CNA, Thorsteinsdottir, U, Chasman, DI, Rotter, JI, Franks, PW, Ripatti, S, Cupples, AL, Sandhu, MS, Rich, SS, Boehnke, M, Deloukas, P, Kathiresan, S, Mohlke, KL, Ingelsson, E, Abecasis, GR |
Corporate/Institutional Authors | Global Lipids Genetics Consortium |
Journal | Nat Genet |
Volume | 45 |
Issue | 11 |
Pagination | 1274-1283 |
Date Published | 2013 Nov |
ISSN | 1546-1718 |
Keywords | African Continental Ancestry Group, Asian Continental Ancestry Group, Cholesterol, HDL, Cholesterol, LDL, Coronary Artery Disease, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lipids, Triglycerides |
Abstract | <p>Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.</p> |
DOI | 10.1038/ng.2797 |
Alternate Journal | Nat. Genet. |
PubMed ID | 24097068 |
PubMed Central ID | PMC3838666 |
Grant List | CZB/4/710 / / Chief Scientist Office / United Kingdom CZB/4/672 / / Chief Scientist Office / United Kingdom RG/08/008/25291 / / British Heart Foundation / United Kingdom R01 HL109946 / HL / NHLBI NIH HHS / United States RG/08/014/24067 / / British Heart Foundation / United Kingdom R01 DK072193 / DK / NIDDK NIH HHS / United States MC_U950080926 / / Medical Research Council / United Kingdom G1000143 / / Medical Research Council / United Kingdom UL1 TR000124 / TR / NCATS NIH HHS / United States MR/L003120/1 / / Medical Research Council / United Kingdom R01 HL105756 / HL / NHLBI NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States MC_U123092720 / / Medical Research Council / United Kingdom MC_U106179472 / / Medical Research Council / United Kingdom G0401527 / / Medical Research Council / United Kingdom G0901213 / / Medical Research Council / United Kingdom 100891 / / Wellcome Trust / United Kingdom 090532 / / Wellcome Trust / United Kingdom R00 HL094535 / HL / NHLBI NIH HHS / United States MR/K013351/1 / / Medical Research Council / United Kingdom PG/08/094/26019 / / British Heart Foundation / United Kingdom P30 DK020572 / DK / NIDDK NIH HHS / United States G0801566 / / Medical Research Council / United Kingdom MC_U106188470 / / Medical Research Council / United Kingdom U01 HL069757 / HL / NHLBI NIH HHS / United States |