Common variants associated with plasma triglycerides and risk for coronary artery disease Journal Article

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Authors: Do, R.; Willer, C. J.; Schmidt, E. M.; Sengupta, S.; Gao, C; 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.; 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.; Altshuler, D.; 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; Mohlke, K. L.; Ingelsson, E; Abecasis, G. R.; Daly, M. J.; Neale, B. M.; Kathiresan, S.
Article Title: Common variants associated with plasma triglycerides and risk for coronary artery disease
Abstract: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
Journal Title: Nature genetics
Volume: 45
Issue: 11
ISSN: 1546-1718; 1061-4036
Publisher: Unknown  
Journal Place: United States
Date Published: 2013
Start Page: 1345
End Page: 1352
Language: eng
DOI/URL:

10.1038/ng.2795
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: 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: R01 DK072193/DK/NIDDK NIH HHS/United States; GR: R01 HL105756/HL/NHLBI NIH HHS/United States; GR: R01 HL107816/HL/NHLBI NIH HHS/United States; GR: R01HL107816/HL/NHLBI NIH HHS/United States; GR: RG/08/014/24067/British Heart Foundation/United Kingdom; GR: T32HL007208/HL/NHLBI NIH HHS/United States; GR: U01 HL069757/HL/NHLBI NIH HHS/United States; GR: UL1 TR000124/TR/NCATS NIH HHS/United States; GR: Canadian Institutes of Health Research/Canada; JID: 9216904; 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Triglycerides); NIHMS524704; OID: NLM: NIHMS524704; OID: NLM: PMC3904346; 2013/02/20 [received]; 2013/09/13 [accepted]; 2013/10/06 [aheadofprint]; ppublish