Association study of MC4R with complex obesity and replication of the rs17782313 association signal

Recently, genome-wide association studies have discovered several single nucleotide polymorphisms (SNPs) involved in the etiology of complex obesity. A variant downstream from the melanocortin-4 receptor gene (MC4R), a gene known to be involved in monogenic obesity, was reported to be highly associated with BMI. In the present study, we performed a replication study with the previously reported SNP rs17782313. We also included 3 tagSNPs (rs8087522, rs11872992, and rs1943226) for the MC4R gene region in our study to understand the role of this gene in complex obesity. We genotyped all 4 SNPs in a population of 1049 obese cases (mean BMI = 38.2 ± 6.2) and 312 healthy lean individuals (mean BMI 22.0 ± 1.7). We could confirm that rs17782313 is highly associated with complex obesity in our population (odds ratio = 1.42, 95% CI 1.14–1.77, P = 0.002). Furthermore, we found this SNP to be associated with BMI (B = 0.92, 95% CI 0.19–1.65, P = 0.01) and body weight (B = 2.44, 95% CI 0.28–4.60, P = 0.03). In addition, we could also detect an association between rs11872992 and complex obesity (odds ratio = 0.74, 95% CI 0.57–0.98, P = 0.03). Through conditional analysis, we demonstrate that this effect is independent from the rs17782313 association signal. No associations with obesity could be found for rs8087522 and rs1943226.In conclusion, we could replicate the previously reported association between rs17782313 and complex obesity. Furthermore, our data do not support the hypothesis that a SNP in MC4R causes the rs17782313 association signal.