Pulse lineResearch With Heart Logo

A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium.

TitleA bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium.
Publication TypeJournal Article
Year of Publication2011
AuthorsKraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ, Sovio U, Mathias RA, Sun YV, Franceschini N, Absher D, Li G, Zhang Q, Feitosa MF, Glazer NL, Haritunians T, Hartikainen A-L, Knowles JW, North KE, Iribarren C, Kral B, Yanek L, O'Reilly PF, McCarthy MI, Jaquish C, Couper DJ, Chakravarti A, Psaty BM, Becker LC, Province MA, Boerwinkle E, Quertermous T, Palotie L, Jarvelin M-R, Becker DM, Kardia SLR, Rotter JI, Chen Y-D I, Borecki IB
JournalDiabetes
Volume60
Issue4
Pagination1329-39
Date Published2011 Apr
ISSN1939-327X
KeywordsAdult, Aged, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Meta-Analysis as Topic, Metabolic Syndrome, Middle Aged, Phenotype, Polymorphism, Single Nucleotide
Abstract

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 ∼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 ∼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.

DOI10.2337/db10-1011
Alternate JournalDiabetes
PubMed ID21386085
PubMed Central IDPMC3064107
Grant ListR01 MH063706 / MH / NIMH NIH HHS / United States
R01-HL-086694 / HL / NHLBI NIH HHS / United States
M01RR00425 / RR / NCRR NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
RL1 MH083268 / MH / NIMH NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
5R01-HL-087679-02 / HL / NHLBI NIH HHS / United States
HL-087660 / HL / NHLBI NIH HHS / United States
R01 HL087698 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01 HL087647 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
5R01-HL-087698 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
1RL1-MH-083268-01 / MH / NIMH NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 HL087679 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
U01-HL-075572 / HL / NHLBI NIH HHS / United States
R01-HL-087641 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
5R01-MH-63706:0 / MH / NIMH NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HL075572 / HL / NHLBI NIH HHS / United States
R01-HL-087652 / HL / NHLBI NIH HHS / United States
U01-HL-080295 / HL / NHLBI NIH HHS / United States
HL-087700 / HL / NHLBI NIH HHS / United States
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
L1-RR-025005 / RR / NCRR NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
R01-HL-59367 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
HL-0877700 / HL / NHLBI NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
090532 / WT_ / Wellcome Trust / United Kingdom
N01-HC-75150 / HC / NHLBI NIH HHS / United States
NC01-HC-55021 / HC / NHLBI NIH HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
DK-063491 / DK / NIDDK NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
HL-087652 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 HL087700 / HL / NHLBI NIH HHS / United States
5R01-HL-087647 / HL / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States