Genome-wide linkage and association analyses to identify genes influencing adiponectin levels

The GEMS study

Hua Ling, Dawn M. Waterworth, Heide A. Stirnadel, Toni I. Pollin, Philip J. Barter, Y. Antero Kesäniemi, Robert W. Mahley, Ruth McPherson, Gérard Waeber, Thomas P. Bersot, Jonathan C Cohen, Scott M Grundy, Vincent E. Mooser, Braxton D. Mitchell

Research output: Contribution to journalArticle

122 Citations (Scopus)

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 × 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.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalObesity
Volume17
Issue number4
DOIs
StatePublished - Apr 2009

Fingerprint

Genome-Wide Association Study
Adiponectin
Single Nucleotide Polymorphism
Genes
Chromosomes
Genome
Molecular Epidemiology
Linkage Disequilibrium
Dyslipidemias
Insulin Resistance
Atherosclerosis
Obesity
Molecular Weight
Lipids
Health

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Ling, H., Waterworth, D. M., Stirnadel, H. A., Pollin, T. I., Barter, P. J., Kesäniemi, Y. A., ... Mitchell, B. D. (2009). Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: The GEMS study. Obesity, 17(4), 737-744. https://doi.org/10.1038/oby.2008.625

Genome-wide linkage and association analyses to identify genes influencing adiponectin levels : The GEMS study. / Ling, Hua; Waterworth, Dawn M.; Stirnadel, Heide A.; Pollin, Toni I.; Barter, Philip J.; Kesäniemi, Y. Antero; Mahley, Robert W.; McPherson, Ruth; Waeber, Gérard; Bersot, Thomas P.; Cohen, Jonathan C; Grundy, Scott M; Mooser, Vincent E.; Mitchell, Braxton D.

In: Obesity, Vol. 17, No. 4, 04.2009, p. 737-744.

Research output: Contribution to journalArticle

Ling, H, Waterworth, DM, Stirnadel, HA, Pollin, TI, Barter, PJ, Kesäniemi, YA, Mahley, RW, McPherson, R, Waeber, G, Bersot, TP, Cohen, JC, Grundy, SM, Mooser, VE & Mitchell, BD 2009, 'Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: The GEMS study', Obesity, vol. 17, no. 4, pp. 737-744. https://doi.org/10.1038/oby.2008.625
Ling H, Waterworth DM, Stirnadel HA, Pollin TI, Barter PJ, Kesäniemi YA et al. Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: The GEMS study. Obesity. 2009 Apr;17(4):737-744. https://doi.org/10.1038/oby.2008.625
Ling, Hua ; Waterworth, Dawn M. ; Stirnadel, Heide A. ; Pollin, Toni I. ; Barter, Philip J. ; Kesäniemi, Y. Antero ; Mahley, Robert W. ; McPherson, Ruth ; Waeber, Gérard ; Bersot, Thomas P. ; Cohen, Jonathan C ; Grundy, Scott M ; Mooser, Vincent E. ; Mitchell, Braxton D. / Genome-wide linkage and association analyses to identify genes influencing adiponectin levels : The GEMS study. In: Obesity. 2009 ; Vol. 17, No. 4. pp. 737-744.
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