Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals (original) (raw)

Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5610 28 -1.2610 243 ). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p,3610 24 ). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3610 23 , n = 22,044), increased triglycerides (p = 2.6610 214 , n = 93,440), increased waist-to-hip ratio (p = 1.8610 25 , n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4610 23 , n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDLcholesterol concentrations (p = 4.5610 213 , n = 96,748) and decreased BMI (p = 1.4610 24 , n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

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References (67)

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