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 SAGE 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 SAGE 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.