期刊
DIABETES
卷 60, 期 4, 页码 1329-1339出版社
AMER DIABETES ASSOC
DOI: 10.2337/db10-1011
关键词
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资金
- National Institutes of Health (NIH) [STAMPEED HL-087700, ADVANCE 5R01-HL-087647, ARIC U01-HL-075572, CHS HL-087652, FHS HL-0877700, GeneSTAR 5R01-HL-087698, GENOA HL-087660, NFBC1RL1-MH-083268-01, HHSN268200625226C, UL1-RR-025005]
- NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018]
- National Human Genome Research Institute [U01HG004402]
- National Institute of Neurologic Disorders and Stroke
- National Center for Research Resources [M01RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-063491]
- Academy of Finland, Center of Excellence in Complex Disease Genetics [104781, 120315]
- University Hospital Oulu, Biocenter
- University of Oulu, Finland
- European Commission [QLG1-CT-2000-01643]
- NIH/NIMH [5R01-MH-63706:02]
- ENGAGE [HEALTH-F4-2007-201413]
- Medical Research Council [G0500539]
- Academy of Finland and Biocentrum Helsinki
- Medical Research Council [G0801056B] Funding Source: researchfish
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
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