Deep resequencing unveils genetic architecture of ADIPOQ and identifies a novel low-frequency variant strongly associated with adiponectin variation.

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Serval ID
serval:BIB_D3900AE55AAF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Deep resequencing unveils genetic architecture of ADIPOQ and identifies a novel low-frequency variant strongly associated with adiponectin variation.
Journal
Diabetes
Author(s)
Warren L.L., Li L., Nelson M.R., Ehm M.G., Shen J., Fraser D.J., Aponte J.L., Nangle K.L., Slater A.J., Woollard P.M., Hall M.D., Topp S.D., Yuan X., Cardon L.R., Chissoe S.L., Mooser V., Morris A.D., Palmer C.N., Perry J.R., Frayling T.M., Whittaker J.C., Waterworth D.M.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
2012
Volume
61
Number
5
Pages
1297-1301
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish. PDF type: Brief report
Abstract
Increased adiponectin levels have been shown to be associated with a lower risk of type 2 diabetes. To understand the relations between genetic variation at the adiponectin-encoding gene, ADIPOQ, and adiponectin levels, and subsequently its role in disease, we conducted a deep resequencing experiment of ADIPOQ in 14,002 subjects, including 12,514 Europeans, 594 African Americans, and 567 Indian Asians. We identified 296 single nucleotide polymorphisms (SNPs), including 30 amino acid changes, and carried out association analyses in a subset of 3,665 subjects from two independent studies. We confirmed multiple genome-wide association study findings and identified a novel association between a low-frequency SNP (rs17366653) and adiponectin levels (P = 2.2E-17). We show that seven SNPs exert independent effects on adiponectin levels. Together, they explained 6% of adiponectin variation in our samples. We subsequently assessed association between these SNPs and type 2 diabetes in the Genetics of Diabetes Audit and Research in Tayside Scotland (GO-DARTS) study, comprised of 5,145 case and 6,374 control subjects. No evidence of association with type 2 diabetes was found, but we were also unable to exclude the possibility of substantial effects (e.g., odds ratio 95% CI for rs7366653 [0.91-1.58]). Further investigation by large-scale and well-powered Mendelian randomization studies is warranted.
Keywords
Adiponectin/blood, Adiponectin/genetics, Base Sequence, Computational Biology, Continental Population Groups, Diabetes Mellitus, Type 2/genetics, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2013 19:57
Last modification date
20/08/2019 15:53
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