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Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

TitleNovel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
Publication TypeJournal Article
Year of Publication2012
AuthorsDastani Z, Hivert M-F, Timpson N, et al.
Secondary AuthorsKathiresan S
Corporate AuthorsDIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC Investigators, GLGC Consortium
JournalPLoS Genet
Volume8
Issue3
Paginatione1002607
Date Published2012
ISSN1553-7404
KeywordsAdiponectin, African Americans, Asian Continental Ancestry Group, Cholesterol, HDL, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio
Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

DOI10.1371/journal.pgen.1002607
Alternate JournalPLoS Genet
PubMed ID22479202
PubMed Central IDPMC3315470
Grant ListG0800582 / MRC_ / Medical Research Council / United Kingdom
MC_U127592696 / MRC_ / Medical Research Council / United Kingdom
N01HC55020 / HL / NHLBI NIH HHS / United States
M01-RR00425 / RR / NCRR NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
DK078150 / DK / NIDDK NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
CZB/4/710 / CSO_ / Chief Scientist Office / United Kingdom
RC2 HL102419 / HL / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
G0801056 / MRC_ / Medical Research Council / United Kingdom
P30 ES010126 / ES / NIEHS NIH HHS / United States
MC_UP_A620_1015 / MRC_ / Medical Research Council / United Kingdom
N01HC95160 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01-HL085251 / HL / NHLBI NIH HHS / United States
G0600705 / MRC_ / Medical Research Council / United Kingdom
MC_UP_A100_1003 / MRC_ / Medical Research Council / United Kingdom
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
G19/35 / MRC_ / Medical Research Council / United Kingdom
PG/09/002/26056 / BHF_ / British Heart Foundation / United Kingdom
N01 AG062101 / AG / NIA NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
G0100222 / MRC_ / Medical Research Council / United Kingdom
R01 HL059367 / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
MC_U127561128 / MRC_ / Medical Research Council / United Kingdom
N01-HC-95163 / HC / NHLBI NIH HHS / United States
G0700931 / MRC_ / Medical Research Council / United Kingdom
N01 HC015103 / HC / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
092731 / WT_ / Wellcome Trust / United Kingdom
R01 DK072193 / DK / NIDDK NIH HHS / United States
/ CAPMC / CIHR / Canada
R01 HL086694 / HL / NHLBI NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
G8802774 / MRC_ / Medical Research Council / United Kingdom
G1000143 / MRC_ / Medical Research Council / United Kingdom
1R01AG032098-01A1 / AG / NIA NIH HHS / United States
G0902037 / MRC_ / Medical Research Council / United Kingdom
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
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MC_U137686857 / MRC_ / Medical Research Council / United Kingdom
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DHCS/07/07/008 / DH_ / Department of Health / United Kingdom
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MC_U106179471 / MRC_ / Medical Research Council / United Kingdom
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MC_PC_U127592696 / MRC_ / Medical Research Council / United Kingdom
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
G0401527 / MRC_ / Medical Research Council / United Kingdom
N01-HC-95164 / HC / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
G0701863 / MRC_ / Medical Research Council / United Kingdom
G0901213 / MRC_ / Medical Research Council / United Kingdom
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K08 DK002600 / DK / NIDDK NIH HHS / United States
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N01-HC-55020 / HC / NHLBI NIH HHS / United States
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UL1 TR000454 / TR / NCATS NIH HHS / United States
090532 / WT_ / Wellcome Trust / United Kingdom
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom
G20234 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
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/ ImNIH / Intramural NIH HHS / United States
064890 / WT_ / Wellcome Trust / United Kingdom
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PG/08/094/26019 / BHF_ / British Heart Foundation / United Kingdom
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MC_U147585824 / MRC_ / Medical Research Council / United Kingdom
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081682 / WT_ / Wellcome Trust / United Kingdom
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R69/0208 / DMT_ / The Dunhill Medical Trust / United Kingdom
N01 HC095159 / HC / NHLBI NIH HHS / United States
N01-HC-95167 / HC / NHLBI NIH HHS / United States
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N01-HC-65226 / HC / NHLBI NIH HHS / United States
G0900339 / MRC_ / Medical Research Council / United Kingdom
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RG/07/008/23674 / BHF_ / British Heart Foundation / United Kingdom