TY - JOUR
T1 - Genome-wide linkage and association analyses to identify genes influencing adiponectin levels
T2 - The GEMS study
AU - Ling, Hua
AU - Waterworth, Dawn M.
AU - Stirnadel, Heide A.
AU - Pollin, Toni I.
AU - Barter, Philip J.
AU - Kesäniemi, Y. Antero
AU - Mahley, Robert W.
AU - McPherson, Ruth
AU - Waeber, Gérard
AU - Bersot, Thomas P.
AU - Cohen, Jonathan C
AU - Grundy, Scott M
AU - Mooser, Vincent E.
AU - Mitchell, Braxton D.
PY - 2009/4
Y1 - 2009/4
N2 - 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 × 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.
AB - 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 × 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.
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U2 - 10.1038/oby.2008.625
DO - 10.1038/oby.2008.625
M3 - Article
C2 - 19165155
AN - SCOPUS:63049113635
SN - 1930-7381
VL - 17
SP - 737
EP - 744
JO - Obesity
JF - Obesity
IS - 4
ER -