title: Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Dorajoo
authors.forename: A I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: X
authors.initials: X
authors.lastname: Sim
authors.forename: R T-H
authors.initials: RT
authors.lastname: Ong
authors.forename: D P K
authors.initials: DP
authors.lastname: Ng
authors.forename: M
authors.initials: M
authors.lastname: Seielstad
authors.forename: T-Y
authors.initials: TY
authors.lastname: Wong
authors.forename: S-M
authors.initials: SM
authors.lastname: Saw
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: E-S
authors.initials: ES
authors.lastname: Tai
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002681:China / Q000208:ethnology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004261:DNA Replication; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India / Q000208:ethnology; D008296:Malaysia / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D009765:Obesity / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D020917:Receptor, trkA / Q000378:metabolism; D015398:Signal Transduction; D012846:Singapore / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D009414:Nerve Growth Factors; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D020917:Receptor, trkA