Objective:SH2B1 has been identified as an interesting candidate gene for complex obesity through genome-wide association studies. Therefore, we set out to replicate the reported association with rs7498665 in our Belgian study population and to extend our study with an additional tagSNP for the SH2B1 gene region. Methods: We genotyped both rs7498665 and rs7201929 in a population of 1,045 obese adults and 317 healthy lean individuals. Statistical analyses were performed to evaluate the role of these polymorphisms in the development of obesity. Results: We found that the rs7498665 minor allele increases obesity risk by 26% (ORage-sex adj = 1.26, 95% CI 1.04–1.52, nominal p = 0.016). Logistic regression showed that the rs7201929 minor allele decreases obesity risk by 24% in the population investigated (ORage-sex adj = 0.76, 95% CI 0.61–0.94, nominal p = 0.011). Conditional analyses showed that both associations represent the same association signal (rs7498665 ORadjusted for rs7201929 = 1.17, 95% CI 0.95–1.45, nominal P = 0.14; rs7201929 ORadjusted for rs7498665 = 0.82, 95% CI 0.65–1.04, nominal p = 0.10). Conclusion: With the current study we were able to replicate and confirm that the SH2B1 gene locus is significantly associated with complex obesity in a Caucasian population.

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