Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study.

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Serval ID
serval:BIB_3BCA4B7CD7C8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study.
Journal
Obesity
Author(s)
Ling H., Waterworth D.M., Stirnadel H.A., Pollin T.I., Barter P.J., Kesäniemi Y.A., Mahley R.W., McPherson R., Waeber G., Bersot T.P., Cohen J.C., Grundy S.M., Mooser V.E., Mitchell B.D.
ISSN
1930-7381
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
17
Number
4
Pages
737-744
Language
english
Abstract
Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10(-7)). These two SNPs were in high linkage disequilibrium (r(2) = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 x 10(-5)) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined.
Keywords
Adiponectin/genetics, Adult, Cadherins/genetics, Europe, Female, Genome-Wide Association Study, Humans, Linkage (Genetics)/genetics, Linkage Disequilibrium/genetics, Male, Metabolic Syndrome X/ethnology, Metabolic Syndrome X/genetics, Middle Aged, Polymorphism, Single Nucleotide/genetics, Turkey
Pubmed
Web of science
Open Access
Yes
Create date
09/02/2010 13:17
Last modification date
20/08/2019 13:31
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