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Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.

TitleExome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology.
Publication TypeJournal Article
Year of Publication2019
AuthorsSpracklen CN, Karaderi T, Yaghootkar H, et al.
Secondary AuthorsMohlke KL
JournalAm J Hum Genet
Volume105
Issue1
Pagination15-28
Date Published2019 07 03
ISSN1537-6605
KeywordsAdiponectin, Adipose Tissue, Adolescent, Adult, African Americans, Aged, Aged, 80 and over, European Continental Ancestry Group, Exome, Female, Genetic Predisposition to Disease, Hispanic Americans, Humans, Lipids, Male, Middle Aged, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Young Adult
Abstract

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p

DOI10.1016/j.ajhg.2019.05.002
Alternate JournalAm J Hum Genet
PubMed ID31178129
PubMed Central IDPMC6612516
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
R01 DK110113 / DK / NIDDK NIH HHS / United States
R01 DK107786 / DK / NIDDK NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
P30 DK056350 / DK / NIDDK NIH HHS / United States
U01 DK105561 / DK / NIDDK NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
R01 DK093757 / DK / NIDDK NIH HHS / United States
P50 HD028138 / HD / NICHD NIH HHS / United States
U01 HG007416 / HG / NHGRI NIH HHS / United States
T32 GM067553 / GM / NIGMS NIH HHS / United States
KL2 TR001109 / TR / NCATS NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
F31 HG009850 / HG / NHGRI NIH HHS / United States
WT098381 / WT_ / Wellcome Trust / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
WT083442AIA / WT_ / Wellcome Trust / United Kingdom
P30 DK020572 / DK / NIDDK NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
R01 HD057194 / HD / NICHD NIH HHS / United States