Genomic variants at 20p11 associated with body fat mass in the European population

Autor: An-Ping Feng, Lu Liu, Yonghong Zhang, Xiao Li, Wen-Zhu Hu, Lei Zhang, Hui Shen, Haigang Ren, Wei-Wen Kong, Yun Huang, Hong-Wen Deng, Chen Fang, Wen Zhao, Yu-Fang Pei, Qing Tian, Xin-Yi You
Rok vydání: 2017
Předmět:
Zdroj: Obesity. 25:757-764
ISSN: 1930-7381
Popis: OBJECTIVE Body fat mass (BFM) is more homogeneous and accurate than body total mass in measuring obesity but has rarely been studied. Aiming to uncover the genetic basis of fat-induced obesity, a genome-wide association meta-analysis of BFM, after adjustment by body lean mass, was performed in the European population. METHODS Three samples of European ancestry were included in the meta-analysis: the Framingham Heart Study (N = 6,004), the Kansas City osteoporosis study (N = 2,207), and the Omaha osteoporosis study (N = 968). RESULTS At the genome-wide significance level (α = 5.0×10-8 ), a cluster of 10 single-nucleotide polymorphisms (SNPs) at chromosomal region 20p11 that were associated with BFM (lead SNP rs2069126, P = 1.82×10-9 , closest gene SLC24A3) was identified in 9,179 subjects. One of the top SNPs, rs6046308 (P = 3.74×10-8 ), was found to be nominally significant for body fat percentage in another independent study (P = 0.03, N = 75,888) and was reported to transregulate the expression of the MPZ gene at 1q23.3 (unadjusted P = 9.78×10-6 , N = 1,490). Differential gene expression analysis demonstrated that SLC24A3 and CFAP61 at the identified locus were differentially expressed in tissues of people with versus without obesity (P = 3.40×10-5 and 8.72×10-4 , N = 126 and 70), implying their potential role in fat development. CONCLUSIONS These results may provide new insights into the biological mechanism that underlies fat-induced obesity pathology.
Databáze: OpenAIRE