Gao Y, Wang B Q, Gao W J, Cao W H, Yu C Q, Lyu J, Wang S F, Pang Z C, Cong L M, Wang H, Wu X P, Liang L M, Li L M
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2017 Feb 6;51(2):137-142. doi: 10.3760/cma.j.issn.0253-9624.2017.02.008.
To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis. A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status. Association analyses between DNA methylation and BMI and between CpGs and cis-SNP were conducted. With rs748212 as the instrumental variable, the association between cg15053022 and BMI was explored using the Mendelian randomization method. A total of 469 participants were selected. The mean age of participants was (44.8±13.2) years and the BMI was (25.0±3.8) kg/m(2). Nine BMI-related DNA methylation sites were found and DNA methylation site cg15053022 in the ATP4A gene was negatively associated with cis-SNP rs748212 (β=-0.020); the mean methylation level of AA, AC, and CC were 0.212±0.025, 0.242±0.024, and 0.264±0.028, respectively. rs748212 was associated with BMI (β=0.04, 0.007) and closely related to cg15053022 (237.66, 0.143). Mendelian randomization analysis showed lower methylation levels at cg15053022 were associated with higher BMI (β=-1.97, 0.001). This study supported the impact of cg15053022 methylation in the ATP4A gene on BMI using Mendelian randomization analysis and provided the basis for using Mendelian randomization analysis in methylation studies.
利用孟德尔随机化分析探讨DNA甲基化与体重指数（BMI）之间的关联。2013年从中国国家双胞胎登记处选取了469名参与者，他们居住在山东、江苏、浙江和四川省，年龄至少18岁。进行了问卷调查和体格检查以收集人口统计学、临床和行为信息。采集外周血细胞以检测基因型和甲基化状态。进行了DNA甲基化与BMI之间以及CpG与顺式SNP之间的关联分析。以rs748212作为工具变量，采用孟德尔随机化方法探讨cg15053022与BMI之间的关联。共选取了469名参与者。参与者的平均年龄为（44.8±13.2）岁，BMI为（25.0±3.8）kg/m²。发现了9个与BMI相关的DNA甲基化位点，ATP4A基因中的DNA甲基化位点cg15053022与顺式SNP rs748212呈负相关（β=-0.020）；AA、AC和CC的平均甲基化水平分别为0.212±0.025、0.242±0.024和0.264±0.028。rs748212与BMI相关（β=0.04，0.007），且与cg15053022密切相关（237.66，0.143）。孟德尔随机化分析表明，cg15053022处较低的甲基化水平与较高的BMI相关（β=-1.97，0.001）。本研究通过孟德尔随机化分析支持了ATP4A基因中cg15053022甲基化对BMI的影响，并为在甲基化研究中使用孟德尔随机化分析提供了依据。
