Discovery and refinement of loci associated with lipid levels.

MedStar author(s):
Citation: Nature Genetics. 45(11):1274-83, 2013 Nov.PMID: 24097068Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Coronary Artery Disease/bl [Blood] | *Coronary Artery Disease/ge [Genetics] | *Lipids/bl [Blood] | *Lipids/ge [Genetics] | African Continental Ancestry Group/ge [Genetics] | Asian Continental Ancestry Group/ge [Genetics] | Cholesterol, HDL/bl [Blood] | Cholesterol, HDL/ge [Genetics] | Cholesterol, LDL/bl [Blood] | Cholesterol, LDL/ge [Genetics] | European Continental Ancestry Group/ge [Genetics] | Genetic Predisposition to Disease | Genome-Wide Association Study | Genotype | Humans | Triglycerides/bl [Blood] | Triglycerides/ge [Genetics]Year: 2013ISSN:
  • 1061-4036
Name of journal: Nature geneticsAbstract: 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.All authors: Abecasis GR, Absher D, Adair LS, Arveiler D, Asiki G, Assimes TL, Bandinelli S, Barroso I, Beckmann JS, Been LF, Bennett F, Bochud M, Boehm BO, Boehnke M, Boerwinkle E, Bolton JL, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Bragg-Gresham JL, Brambilla P, Buchkovich ML, Burnett MS, Burnier M, Campbell H, Cesana G, Chakravarti A, Chambers JC, Chang HY, Chasman DI, Chen J, Chen YD, Collins FS, Cooper RS, Cupples LA, Danesh J, de Faire U, Dedoussis G, Deloukas P, Demirkan A, Den Hertog HM, Dimitriou M, Do R, Doney AS, Donnelly LA, Doring A, Ehret GB, Elliott P, Epstein SE, Esko T, Eyjolfsson GI, Feitosa MF, Feranil AB, Ferreira T, Ferrieres J, Ferrucci L, Fischer K, Fontanillas P, Franks PW, Fraser RM, Freimer NB, Freitag DF, Ganna A, Gieger C, Gigante B, Global Lipids Genetics Consortium, Goodarzi MO, Grallert H, Gravito ML, Groop LC, Groves CJ, Gudnason V, Gurdasani D, Gustafsson S, Gyllensten U, Hallmans G, Hamsten A, Harris TB, Hartikainen AL, Hayward C, Heikkila K, Hernandez D, Hicks AA, Hingorani A, Hirschhorn JN, Hofman A, Holm H, Hovingh GK, Hsiung CA, Humphries SE, Hung YJ, Hunt SC, Hveem K, Hypponen E, Illig T, Ingelsson E, Iribarren C, Isaacs A, Jackson AU, Jarvelin MR, Johansson A, Johnson T, Jones MR, Jula A, Kaakinen M, Kahonen M, Kaleebu P, Kanoni S, Kaprio J, Kastelein JJ, Kathiresan S, Kesaniemi A, Kettunen J, Khaw KT, Kim E, Kivimaki M, Kleber ME, Klopp N, Komulainen P, Kooner JS, Koudstaal PJ, Krauss RM, Kuh D, Kumari M, Kuusisto J, Kyvik KO, Laakso M, Lakka TA, Langenberg C, Lehtimaki T, Li X, Lin SY, Lind L, Lindgren CM, Lindstrom J, Loos RJ, Luan J, Lyytikainen LP, Mach F, Magnusson PK, Mangino M, Martin NG, Marz W, McArdle WL, McCarthy MI, McKenzie CA, Meisinger C, Meneton P, Metspalu A, Mihailov E, Mitchell BD, Mohlke KL, Moilanen L, Montasser ME, Mora S, Morris AD, Muller G, Muller-Nurasyid M, Munroe PB, Nagaraja R, Narisu N, Nieminen TV, Njolstad I, Nolte IM, Nsubuga RN, O'Connell JR, Olafsson I, Ong KK, Ordovas JM, Palmer CD, Palmer CN, Palotie A, Papamarkou T, Pedersen NL, Peloso GM, Perola M, Petersen AK, Pomilla C, Pouta A, Power C, Pramstaller PP, Price JF, Psaty BM, Quertermous T, Rader DJ, Rauramaa R, Reilly MP, Rich SS, Ridker PM, Ripatti S, Rivadeneira F, Rotter JI, Rudan I, Ruokonen A, Saleheen D, Salomaa V, Samani N, Sandhu MS, Sanghera DK, Sanna S, Saramies J, Saxena R, Scharnagl H, Schmidt EM, Schwarz PE, Seeley J, Sengupta S, Service SK, Shah S, Sheu WH, Shuldiner AR, Shungin D, Sidore C, Siegbahn A, Silander K, Song C, Spector TD, Stancakova A, Stefansson K, Stirrups K, Strachan DP, Strawbridge RJ, Surakka I, Swift AJ, Tanaka T, Tayo BO, Teslovich TM, Thorleifsson G, Thorsteinsdottir U, Tiret L, Tremoli E, Tuomilehto J, Uitterlinden AG, Uusitupa M, Van den Herik EG, van Duijn CM, van Pelt LJ, Vedantam S, Voight BF, Volcik KA, Vollenweider P, Wainwright N, Waite LL, Wallentin L, Wareham NJ, Whitfield JB, Wijmenga C, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, Wolffenbuttel BH, Wong A, Wu Y, Young EH, Zhang W, Zhao JHFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2014-02-24
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Journal Article MedStar Authors Catalog Article 24097068 Available 24097068

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.

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