Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0096149
Title: Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries
Authors: Tan L.-J.
Zhu H.
He H.
Wu K.-H.
Li J.
Chen X.-D.
Zhang J.-G.
Shen H. 
Tian Q.
Krousel-Wood M.
Papasian C.J.
Bouchard C.
Pérusse L.
Deng H.-W.
Keywords: DNA
uncoupling protein 2
ADRB2 gene
African American
article
body fat
body mass
Caucasian
Chinese
CTNNBL1 gene
disease predisposition
DNA polymorphism
ethnic difference
female
FTO gene
gene
gene replication
genetic association
genetic susceptibility
genetic variability
genotype
Hispanic
human
LEPR gene
male
meta analysis
obesity
pathophysiology
phenotype
PPARG gene
sex difference
single nucleotide polymorphism
ucp2 gene
ancestry group
genetic predisposition
genetics
obesity
reproducibility
Continental Population Groups
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Obesity
Phenotype
Reproducibility of Results
Issue Date: 2014
Citation: Tan L.-J., Zhu H., He H., Wu K.-H., Li J., Chen X.-D., Zhang J.-G., Shen H., Tian Q., Krousel-Wood M., Papasian C.J., Bouchard C., Pérusse L., Deng H.-W. (2014). Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries. PLoS ONE 9 (5) : e96149. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0096149
Abstract: Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01 × 10-7 for BMI, 1.80 × 10-6 for FM, and 5.29 × 10-4 for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15 × 10-3 to 4.94 × 10 -2). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized treatment of obesity. © 2014 Tan et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161408
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0096149
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