Common variants associated with plasma triglycerides and risk for coronary artery disease.
Do R., Willer CJ., Schmidt EM., Sengupta S., Gao C., Peloso GM., Gustafsson S., Kanoni S., Ganna A., Chen J., Buchkovich ML., Mora S., Beckmann JS., Bragg-Gresham JL., Chang H-Y., Demirkan A., Den Hertog HM., 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., 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 GI., 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., van Pelt LJ., 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., Ferrières J., Ferrucci L., Freimer NB., Gieger C., Groop LC., Gudnason V., Gyllensten U., Hamsten A., Harris TB., Hingorani A., Hirschhorn JN., Hofman A., Hovingh GK., Hsiung CA., Humphries SE., Hunt SC., Hveem K., Iribarren C., Järvelin 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., Altshuler D., Ordovas JM., Boerwinkle E., Palmer CNA., Thorsteinsdottir U., Chasman DI., Rotter JI., Franks PW., Ripatti S., Cupples LA., Sandhu MS., Rich SS., Boehnke M., Deloukas P., Mohlke KL., Ingelsson E., Abecasis GR., Daly MJ., Neale BM., Kathiresan S.
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 × 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.