A novel locus for body mass index on 5p15.2: a meta-analysis of two genome-wide association studies.

OBJECTIVE:Genetic factors play an important role in modulating the vulnerability to body mass index (BMI). The purpose of this study is to identify novel genetic variants for BMI using genome-wide association (GWA) meta-analysis. METHODS:PLINK software was used to perform meta-analysis of two GWA studies (the FUSION and Marshfield samples) of 5218 Caucasian individuals with BMI. A replication study was conducted using the sample with 762 individuals. RESULTS:Through meta-analysis we identified 33 SNPs associated with BMI with p<10(-4). The most significant association was observed with rs2967951 (p=1.19×10(-6)) at 5p15.2 within ROPN1L gene. Two additional SNPs within ROPN1L and 5 SNPs within MARCH6 (the top SNP was rs2607292 with 4.27×10(-6)) further supported the association with BMI on 5p15.2 (p<1.8×10(-5)). Conditional analysis on 5p15.2 could not distinguish the effects of ROPN1L and MARCH6. Several SNPs within MARCH6 and ROPN1L were replicated in the duanyu1798 sample (p<0.05). CONCLUSION:We identified a novel locus for BMI. These findings offer the potential for new insights into the pathogenesis of BMI and obesity and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in BMI and obesity.

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