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

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. We utilised five GWAS (N=10 482) from Chinese (three cohorts, including one with type 2 diabetes and an...

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Bibliographic Details
Published in:International Journal of Obesity 2012-01, Vol.36 (1), p.159-163
Main Authors: DORAJOO, R, BLAKEMORE, Aif, TAI, E.-S, SIM, X, ONG, Rt-H, NG, Dpk, SEIELSTAD, M, WONG, T.-Y, SAW, S.-M, FROGUEL, P, LIU, J
Format: Article
Language:English
Subjects:
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Analysis
Asian Continental Ancestry Group - genetics
Asians
Biological and medical sciences
Body mass
Body Mass Index
China - ethnology
Cohort Studies
Diabetes
DNA Mutational Analysis
DNA Replication
Ethnic groups
European Continental Ancestry Group - genetics
Female
Genetic aspects
Genetics
Genome-Wide Association Study
Health aspects
Humans
India - ethnology
Malaysia - ethnology
Male
Medical sciences
Meta analysis
Metabolic diseases
Middle Aged
Nerve Growth Factors - metabolism
Obesity
Obesity - epidemiology
Obesity - ethnology
Obesity - genetics
Objectives
Polymorphism, Single Nucleotide
Proteins - genetics
Receptor, trkA - metabolism
Risk factors
Signal Transduction
Singapore - epidemiology
Single nucleotide polymorphisms
Statistics
Systematic review
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Summary: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. 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. 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. 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.
ISSN:0307-0565
1476-5497
DOI:10.1038/ijo.2011.86