title: Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.
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.
authors.affiliation: Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Tan
authors.affiliation: Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Ke-Hao
authors.initials: KH
authors.lastname: Wu
authors.affiliation: School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.affiliation: School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Ji-Gang
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Marie
authors.initials: M
authors.lastname: Krousel-Wood
authors.affiliation: School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America.
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.affiliation: Department of Kinesiology, Laval University, Québec, Québec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.affiliation: Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; School of Public Health and Tropical Medicine and/or School of Medicine, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics*; D015203:Reproducibility of Results