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

Int J Obes (Lond). 2012 Jan;36(1):159-63. doi: 10.1038/ijo.2011.86. Epub 2011 Apr 19.

Abstract

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 × 10(-7)-7.95 × 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 × 10(-4)-1.44 × 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Asians / genetics*
  • Body Mass Index*
  • China / ethnology
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA Replication*
  • Female
  • Genome-Wide Association Study
  • Humans
  • India / ethnology
  • Malaysia / ethnology
  • Male
  • Middle Aged
  • Nerve Growth Factors / metabolism
  • Obesity / epidemiology
  • Obesity / ethnology*
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Receptor, trkA / metabolism
  • Signal Transduction
  • Singapore / epidemiology
  • Whites / genetics*

Substances

  • Nerve Growth Factors
  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • Receptor, trkA