Discovery and refinement of loci associated with lipid levels.
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., Den Hertog HM., 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 Å., 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., Ingi Eyjolfsson G., 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., 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., Kathiresan S., Mohlke KL., Ingelsson E., Abecasis GR., Global Lipids Genetics Consortium None.
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.