Discovery and refinement of loci associated with lipid levels

被引：1299

作者：

Willer, Cristen J. ^{[1
,2
,3
,4
]}

Schmidt, Ellen M. ^{[2
]}

Sengupta, Sebanti ^{[4
]}

Peloso, Gina M. ^{[5
,6
,7
]}

Gustafsson, Stefan ^{[8
,9
]}

Kanoni, Stavroula ^{[10
]}

Ganna, Andrea ^{[8
,9
,11
]}

Chen, Jin ^{[4
]}

Buchkovich, Martin L. ^{[12
]}

Mora, Samia ^{[13
,14
]}

Beckmann, Jacques S. ^{[15
,16
]}

Bragg-Gresham, Jennifer L. ^{[4
]}

Chang, Hsing-Yi ^{[17
]}

Demirkan, Ayse ^{[18
]}

Den Hertog, Heleen M. ^{[19
]}

Do, Ron ^{[6
]}

Donnelly, Louise A. ^{[20
]}

Ehret, Georg B. ^{[21
,22
]}

Esko, Tonu ^{[7
,23
,24
]}

Feitosa, Mary F. ^{[25
]}

Ferreira, Teresa ^{[26
]}

Fischer, Krista ^{[23
]}

Fontanillas, Pierre ^{[7
]}

Fraser, Ross M. ^{[27
]}

Freitag, Daniel F. ^{[28
]}

Gurdasani, Deepti ^{[10
,28
]}

Heikkila, Kauko ^{[29
]}

Hyppoenen, Elina ^{[30
]}

Isaacs, Aaron ^{[18
,31
]}

Jackson, Anne U. ^{[4
]}

Johansson, Asa ^{[32
,33
]}

Johnson, Toby ^{[34
,35
]}

Kaakinen, Marika ^{[36
,37
]}

Kettunen, Johannes ^{[38
,39
]}

Kleber, Marcus E. ^{[40
,41
]}

Li, Xiaohui ^{[42
]}

Luan, Jian'an ^{[43
]}

Lyytikainen, Leo-Pekka ^{[44
,45
]}

Magnusson, Patrik K. E. ^{[11
]}

Mangino, Massimo ^{[46
]}

Mihailov, Evelin ^{[23
,24
]}

Montasser, May E. ^{[47
]}

Mueller-Nurasyid, Martina ^{[48
,49
,50
]}

Nolte, Ilja M. ^{[51
]}

O'Connell, Jeffrey R. ^{[47
]}

Palmer, Cameron D. ^{[7
,52
,53
]}

Perola, Markus ^{[23
,38
,39
]}

Petersen, Ann-Kristin ^{[48
]}

Sanna, Serena ^{[54
]}

Saxena, Richa ^{[6
]}

机构：

[1] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[5] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[6] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[7] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[8] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[9] Uppsala Univ, Sci Life Lab, Uppsala, Sweden

[10] Wellcome Trust Sanger Inst, Hinxton, England

[11] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[12] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[13] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[14] Harvard Univ, Sch Med, Boston, MA USA

[15] Univ Lausanne Hosp, Serv Med Genet, Lausanne, Switzerland

[16] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[17] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Prevent Med & Hlth Serv Res, Zhunan, Taiwan

[18] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands

[19] Erasmus MC, Dept Neurol, Rotterdam, Netherlands

[20] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland

[21] Univ Hosp Geneva, Dept Special Med, Geneva, Switzerland

[22] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA

[23] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[24] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia

[25] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[26] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[27] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[28] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[29] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland

[30] UCL, Inst Child Hlth, MRC, Ctr Paediat Epidemiol & Biostat,Ctr Epidemiol Chi, London, England

[31] Ctr Med Syst Biol, Leiden, Netherlands

[32] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[33] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden

[34] Queen Mary Univ London, Barts & London Sch Med & Dent, Genome Ctr, London, England

[35] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Natl Inst Hlth Res,Cardiovasc Biomed Res Unit, London, England

[36] Univ Oulu, Bioctr Oulu, Oulu, Finland

[37] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[38] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[39] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland

[40] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany

[41] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany

[42] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[43] Addenbrookes Hosp, MRC, Inst Metab Sci, Epidemiol Unit, Cambridge, England

[44] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland

[45] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland

[46] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[47] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[48] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany

[49] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany

[50] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

来源：

NATURE GENETICS | 2013年 / 45卷 / 11期

关键词：

DENSITY-LIPOPROTEIN CHOLESTEROL; HEART-DISEASE; SUSCEPTIBILITY LOCI; IDENTIFIES; 13; RISK; GENE; METAANALYSIS; HOMEOSTASIS; TRAITS; PLASMA;

D O I：

10.1038/ng.2797

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1274 / +

页数：12

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