A Bivariate Genome-Wide Approach to Metabolic Syndrome STAMPEED Consortium

被引：195

作者：

Kraja, Aldi T. ^{[1
]}

Vaidya, Dhananjay ^{[2
]}

Pankow, James S. ^{[3
]}

Goodarzi, Mark O. ^{[4
]}

Assimes, Themistocles L. ^{[5
]}

Kullo, Iftikhar J. ^{[6
]}

Sovio, Ulla ^{[7
]}

Mathias, Rasika A. ^{[2
]}

Sun, Yan V. ^{[8
]}

Franceschini, Nora ^{[9
]}

Absher, Devin ^{[10
]}

Li, Guo ^{[11
,12
]}

Zhang, Qunyuan ^{[1
]}

Feitosa, Mary F. ^{[1
]}

Glazer, Nicole L. ^{[11
,12
]}

Haritunians, Talin ^{[13
]}

Hartikainen, Anna-Liisa ^{[14
]}

Knowles, Joshua W. ^{[5
]}

North, Kari E. ^{[9
,15
]}

Iribarren, Carlos ^{[16
]}

Kral, Brian ^{[2
]}

Yanek, Lisa ^{[2
]}

O'Reilly, Paul F. ^{[17
]}

McCarthy, Mark I. ^{[18
]}

Jaquish, Cashell ^{[19
]}

Couper, David J. ^{[20
,21
]}

Chakravarti, Aravinda ^{[22
]}

Psaty, Bruce M. ^{[23
,24
,25
,26
]}

Becker, Lewis C. ^{[2
]}

Province, Michael A. ^{[1
]}

Boerwinkle, Eric ^{[27
]}

Quertermous, Thomas ^{[5
]}

Palotie, Leena ^{[28
]}

Jarvelin, Marjo-Riitta ^{[17
,29
,30
,31
]}

Becker, Diane M. ^{[2
]}

Kardia, Sharon L. R. ^{[8
]}

Rotter, Jerome I. ^{[13
]}

Chen, Yii-Der Ida ^{[32
]}

Borecki, Ingrid B. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63101 USA

[2] Johns Hopkins Univ, GeneSTAR Res Program, Baltimore, MD USA

[3] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA

[4] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA

[5] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA

[6] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA

[7] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England

[8] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA

[9] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[10] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

[11] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[12] Univ Washington, Dept Med, Seattle, WA 98195 USA

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

[14] Univ Oulu, Inst Clin Med, Oulu, Finland

[15] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA

[16] Kaiser Fdn Res Inst, Oakland, CA USA

[17] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, Fac Med, London, England

[18] Univ Oxford, Churchill Hosp, OCDEM, Oxford, England

[19] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA

[20] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[21] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA

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

[23] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[24] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[25] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[26] Grp Hlth Res Inst, Seattle, WA USA

[27] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[28] Wellcome Trust Sanger Inst, Cambridge, England

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

[30] Univ Oulu, Bioctr Oulu, Oulu, Finland

[31] Natl Inst Hlth & Welf, Oulu, Finland

[32] Univ Calif Los Angeles, Los Angeles, CA USA

来源：

DIABETES | 2011年 / 60卷 / 04期

基金：

芬兰科学院; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; FASTING PLASMA-GLUCOSE; TYPE-2 DIABETES RISK; INSULIN-RESISTANCE; APOLIPOPROTEIN A5; HDL CHOLESTEROL; HEART-DISEASE; MEXICAN-AMERICANS; BLOOD-PRESSURE;

D O I：

10.2337/db10-1011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS-Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of similar to 2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS-Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from similar to 9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS-Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants. Diabetes 60:1329-1339, 2011

引用

页码：1329 / 1339

页数：11

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