Genome-wide association scans identified CTNNBL1 as a novel gene for obesity

• DOI: 10.1093/hmg/ddn072
• Publication Date: 2008-03-07T01:14:13Z
• Authors: Yong-Jun Liu; Xiao-Gang Liu; Liang Wang; Christian Dina; Han Yan; Jian-Feng Liu; Shawn Levy; Christopher J. Pa...; Betty M. Drees; James J. Hamilton; David Meyre; Jerome Delplanque; Yu-Fang Pei; Lei Zhang; Robert R. Recker; Philippe Froguel; Hong-Wen Deng
• Keywords: SNP; Minor allele frequency; Genome-wide Association Study; Genetic Association

Obesity is a major public health problem with strong genetic determination; however, the factors underlying obesity are largely unknown. In this study, we performed genome-wide association scan for by examining approximately 500 000 single-nucleotide polymorphisms (SNPs) in sample of 1000 unrelated US Caucasians. We identified novel gene, CTNNBL1, which has multiple SNPs associated body mass index (BMI) and fat mass. The most significant SNP, rs6013029, achieved experiment-wise P-values 2.69 × 10−7 BMI 4.99 10−8 mass, respectively. SNP rs6013029 minor allele T confers an average increase 2.67 kg/m2 5.96 kg, respectively, compared alternative G. further genotyped five CTNNBL1 French case–control comprising 896 class III obese adults (BMI ≥ 40 kg/m2) 2916 lean < 25 kg/m2). All showed consistent associations (8.83 10−3 P 6.96 10−4). Those subjects who were homozygous had 1.42-fold increased odds those without allele. protein structure homologous to β-catenin, family proteins containing armadillo repeats, suggesting similar biological functions. β-Catenin involved Wnt/β-catenin-signaling pathway appears contribute maintaining undifferentiated state pre-adipocytes inhibiting adipogenic gene expression. Our study hence suggests mechanism development obesity, where may play important role. also provided supportive evidence previously between INSIG2 PFKP, but not FTO.