Discovery and refinement of loci associated with lipid levels Journal Article

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Authors: Global Lipids Genetics Consortium; Willer, C. J.; Schmidt, E. M.; Sengupta, S.; Peloso, G. M.; Gustafsson, S.; Kanoni, S; Ganna, A.; Chen, J; Buchkovich, M. L.; Mora, S.; Beckmann, J. S.; Bragg-Gresham, J. L.; Chang, H. Y.; Demirkan, A; Den Hertog, H. M.; Do, R.; Donnelly, L. A.; Ehret, G. B.; Esko, T; Feitosa, M. F.; Ferreira, T.; Fischer, K; Fontanillas, P.; Fraser, R. M.; Freitag, D. F.; Gurdasani, D.; Heikkila, K.; Hypponen, E.; Isaacs, A; Jackson, A. U.; Johansson, A; Johnson, T; Kaakinen, M.; Kettunen, J.; Kleber, M. E.; Li, X; Luan, J; Lyytikainen, L. P.; Magnusson, P. K.; Mangino, M; Mihailov, E; Montasser, M. E.; Muller-Nurasyid, M.; Nolte, I. M.; O'Connell, J. R.; Palmer, C. D.; Perola, M; Petersen, A. K.; Sanna, S; Saxena, R.; Service, S. K.; Shah, S; Shungin, D.; Sidore, C.; Song, C.; Strawbridge, R. J.; Surakka, I.; Tanaka, T; Teslovich, T. M.; Thorleifsson, G; Van den Herik, E. G.; Voight, B. F.; Volcik, K. A.; Waite, L. L.; Wong, A; Wu, Y; Zhang, W; Absher, D.; Asiki, G; Barroso, I; Been, L. F.; Bolton, J. L.; Bonnycastle, L. L.; Brambilla, P.; Burnett, M. S.; Cesana, G.; Dimitriou, M.; Doney, A. S.; Doring, A.; Elliott, P; Epstein, S. E.; Eyjolfsson, G. I.; Gigante, B; Goodarzi, M. O.; Grallert, H; Gravito, M. L.; Groves, C. J.; Hallmans, G; Hartikainen, A. L.; Hayward, C; Hernandez, D; Hicks, A. A.; Holm, H; Hung, Y. J.; Illig, T; Jones, M. R.; Kaleebu, P.; Kastelein, J. J.; Khaw, K. T.; Kim, E; Klopp, N.; Komulainen, P; Kumari, M; Langenberg, C; Lehtimaki, T.; Lin, S. Y.; Lindstrom, J.; Loos, R. J.; Mach, F.; McArdle, W. L.; Meisinger, C; Mitchell, B. D.; Muller, G.; Nagaraja, R.; Narisu, N; Nieminen, T. V.; Nsubuga, R. N.; Olafsson, I; Ong, K. K.; Palotie, A.; Papamarkou, T.; Pomilla, C.; Pouta, A.; Rader, D. J.; Reilly, M. P.; Ridker, P. M.; Rivadeneira, F; Rudan, I; Ruokonen, A.; Samani, N.; Scharnagl, H.; Seeley, J.; Silander, K.; Stancakova, A.; Stirrups, K.; Swift, A. J.; Tiret, L.; Uitterlinden, A. G.; van Pelt, L. J.; Vedantam, S; Wainwright, N.; Wijmenga, C.; Wild, S. H.; Willemsen, G; Wilsgaard, T.; Wilson, J. F.; Young, E. H.; Zhao, J. H.; Adair, L. S.; Arveiler, D.; Assimes, T. L.; Bandinelli, S; Bennett, F.; Bochud, M; Boehm, B. O.; Boomsma, D. I.; Borecki, I. B.; Bornstein, S. R.; Bovet, P; Burnier, M.; Campbell, H; Chakravarti, A; Chambers, J. C.; Chen, Y. D.; Collins, F. S.; Cooper, R. S.; Danesh, J; Dedoussis, G; de Faire, U; Feranil, A. B.; Ferrieres, J.; Ferrucci, L; Freimer, N. B.; Gieger, C; Groop, L. C.; Gudnason, V; Gyllensten, U; Hamsten, A; Harris, T. B.; Hingorani, A.; Hirschhorn, J. N.; Hofman, A; Hovingh, G. K.; Hsiung, C. A.; Humphries, S. E.; Hunt, S. C.; Hveem, K; Iribarren, C.; Jarvelin, M. R.; Jula, A.; Kahonen, M.; Kaprio, J.; Kesaniemi, A.; Kivimaki, M; Kooner, J. S.; Koudstaal, P. J.; Krauss, R. M.; Kuh, D; Kuusisto, J; Kyvik, K. O.; Laakso, M; Lakka, T. A.; Lind, L; Lindgren, C. M.; Martin, N. G.; Marz, W.; McCarthy, M. I.; McKenzie, C. A.; Meneton, P.; Metspalu, A; Moilanen, L.; Morris, A. D.; Munroe, P. B.; Njolstad, I.; Pedersen, N. L.; Power, C.; Pramstaller, P. P.; Price, J. F.; Psaty, B. M.; Quertermous, T.; Rauramaa, R; Saleheen, D.; Salomaa, V; Sanghera, D. K.; Saramies, J.; Schwarz, P. E.; Sheu, W. H.; Shuldiner, A. R.; Siegbahn, A.; Spector, T. D.; Stefansson, K; Strachan, D. P.; Tayo, B. O.; Tremoli, E; Tuomilehto, J; Uusitupa, M.; van Duijn, C. M.; Vollenweider, P; Wallentin, L; Wareham, N. J.; Whitfield, J. B.; Wolffenbuttel, B. H.; Ordovas, J. M.; Boerwinkle, E; Palmer, C. N.; Thorsteinsdottir, U; Chasman, D. I.; Rotter, J. I.; Franks, P. W.; Ripatti, S.; Cupples, L. A.; Sandhu, M. S.; Rich, S. S.; Boehnke, M; Deloukas, P; Kathiresan, S.; Mohlke, K. L.; Ingelsson, E; Abecasis, G. R.
Article Title: Discovery and refinement of loci associated with lipid levels
Abstract: 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 x 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.
Journal Title: Nature genetics
Volume: 45
Issue: 11
ISSN: 1546-1718; 1061-4036
Publisher: Unknown  
Journal Place: United States
Date Published: 2013
Start Page: 1274
End Page: 1283
Language: eng
DOI/URL:

10.1038/ng.2797
Notes: LR: 20140610; GR: 090532/Wellcome Trust/United Kingdom; GR: CZB/4/672/Chief Scientist Office/United Kingdom; GR: CZB/4/710/Chief Scientist Office/United Kingdom; GR: G0801566/Medical Research Council/United Kingdom; GR: G0901213/Medical Research Council/United Kingdom; GR: G1000143/Medical Research Council/United Kingdom; GR: MC_U106179471/Medical Research Council/United Kingdom; GR: MC_U106179472/Medical Research Council/United Kingdom; GR: MC_U106188470/Medical Research Council/United Kingdom; GR: MC_U123092720/Medical Research Council/United Kingdom; GR: MC_U950080926/Medical Research Council/United Kingdom; GR: P30 DK063491/DK/NIDDK NIH HHS/United States; GR: P30 DK072488/DK/NIDDK NIH HHS/United States; GR: PG/08/094/26019/British Heart Foundation/United Kingdom; GR: R00 HL094535/HL/NHLBI NIH HHS/United States; GR: R01 DK072193/DK/NIDDK NIH HHS/United States; GR: R01 HL105756/HL/NHLBI NIH HHS/United States; GR: R01 HL109946/HL/NHLBI NIH HHS/United States; GR: RG/08/008/25291/British Heart Foundation/United Kingdom; GR: RG/08/014/24067/British Heart Foundation/United Kingdom; GR: U01 HL069757/HL/NHLBI NIH HHS/United States; GR: UL1 TR000124/TR/NCATS NIH HHS/United States; JID: 9216904; 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Lipids); 0 (Triglycerides); NIHMS524703; OID: NLM: NIHMS524703; OID: NLM: PMC3838666; 2012/10/12 [received]; 2013/09/13 [accepted]; 2013/10/06 [aheadofprint]; ppublish