Adiponectin concentrations: a genome-wide association study

Abstract

Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.

Figure 1

Significance of SNPs in CDH13 for All Three Cohorts Discovery set, n = 979; replication set 1, n = 3,022; replication set 2, n = 2,034. Here, a linear regression model including age, gender, smoking status, and body mass index was used for each individual SNP. Top panel: plot showing the −log₁₀(p value). Black, red, and white symbols represent data from the discovery study, replication set 1, and replication set 2, respectively. Bottom panel: plot showing the recombination rate (blue) and cumulative recombination rate measured away from the most highly associated SNP of rs3865188 (yellow). Positions of highly significant SNPs were upstream of CDH13.

Figure 2

–log₁₀(p Value) for both Imputed and Genotyped SNPs in ADIPOQ in 4,001 Korean Adults Red dots are genotyped SNPs; open blue squares are imputed SNPs.