The increasing prevalence of obesity is related to excessive caloric intake and diminished physical activity in the modern environment. However, genetic factors may modulate the impact of the environment in an individual. Considerable evidence from familial segregation and twin studies suggest a significant genetic contribution to BMI (3), with heritability estimates between 60 to 90% in African Americans (4,5). Recently, large-scale genome-wide association studies (GWAS) and meta-analyses conducted in populations of European ancestry revealed over 40 novel adiposity loci associated with BMI, waist circumference, and/or waist-hip-ratio (6–17). Many of these loci have been confirmed in Asian populations by GWAS (18,19) and replication studies (20–22). However, results in other populations are less convincing. Replication studies in African Americans showed a lack of association of MC4R (23) and inconclusive association of FTO (24,25) with adiposity measures. Here, we report a two-stage study including a GWAS of BMI in 1,715 African Americans followed by replication in additional African-American samples.
