Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations

Objective: Recent genome-wide association studies (GWAS) have identified 38 obesity-associated loci among European populations. However, their contribution to obesity in other ethnicities is largely unknown. Methods: We utilised five GWAS (N = 10 482) from Chinese (three cohorts, including one with type 2 diabetes and another one of children), Malay and Indian ethnic groups from Singapore. Data sets were analysed individually and subsequently in combined meta-analysis for Z-score body-mass index (BMI) associations. Results: Variants at the FTO locus showed the strongest associations with BMI Z-score after meta-analysis (P-values 1.16 x 10(-7) - 7.95 x 10(-7)). We further detected associations with nine other index obesity variants close to the MC4R, GNPDA2, TMEM18, QPCTL/GIPR, BDNF, ETV5, MAP2K5/SKOR1, SEC16B and TNKS/MSRA loci (meta-analysis P-values ranging from 3.58 x 10(-4) - 1.44 x 10(-2)). Three other single-nucleotide polymorphisms (SNPs) from CADM2, PTBP2 and FAIM2 were associated with BMI (P-value <= 0.0418) in at least one dataset. The neurotrophin/TRK pathway (P-value = 0.029) was highlighted by pathway-based analysis of loci that had statistically significant associations among Singaporean populations. Conclusion: Our data confirm the role of FTO in obesity predisposition among Chinese, Malays and Indians, the three major Asian ethnic groups. We additionally detected associations for 12 obesity-associated SNPs among Singaporeans. Thus, it is likely that Europeans and Asians share some of the genetic predisposition to obesity. Furthermore, the neurotrophin/TRK signalling may have a central role for common obesity among Asians. International Journal of Obesity (2012) 36, 159-163; doi:10.1038/ijo.2011.86; published online 19 April 2011