Liu X T, Tu R Q, He Y L, Dong X K, Li R Y, Hou J, Li Y Q, Wang C J
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Aug 10;43(8):1315-1320. doi: 10.3760/cma.j.cn112338-20220318-00200.
Based on the Mendelian randomization analysis, to assess the causal relationship between DNA methylation levels of Janus kinase 2 (JAK2) and obesity. A case-control study was carried out, including 1 021 individuals [obesity (visceral fat index ≥10) no obesity (visceral fat index <10) was 440 581] from the Henan Rural Cohort Study. MethylTarget target region methylation sequencing technology was used for testing the DNA methylation level of JAK2. logistic regression models were used to assess the association between the DNA methylation level of JAK2 and obesity. With SNP as the instrumental variable, the association between the DNA methylation level of JAK2 and obesity was explored by using the Mendelian randomization analysis method. There was a positive association between Chr9:4984943 (one DNA methylation site in the promoter of JAK2) and obesity, and the (95%) was 1.22(1.04-1.42). Methylation level of five sites in the exon of JAK2 (Chr9:4985378, Chr9:4985404, Chr9:4985407, Chr9:4985409 and Chr9:4985435) were negatively associated with obesity, the corresponding (95%) were 0.53 (0.29-0.95), 0.58(0.36-0.93), 0.69 (0.49-0.97), 0.72 (0.53-0.99) and 0.58 (0.35-0.98) , respectively. Mendelian randomization analysis showed that there was a causal relationship between the DNA methylation levels of JAK2 and obesity, and the corresponding (95%) were -1.985 (-3.520 - -0.450),-3.547 (-6.301 - -0.792) and -3.900 (-6.328 - -1.472) for Mendelian randomization method of inverse variance weighted, Mendelian randomization method of median based and Maximum-likelihood method, respectively. This study supported there was a causal relationship between the DNA methylation level of JAK2 and obesity.
基于孟德尔随机化分析，评估Janus激酶2（JAK2）的DNA甲基化水平与肥胖之间的因果关系。开展了一项病例对照研究，纳入了来自河南农村队列研究的1021名个体[肥胖（内脏脂肪指数≥10） 非肥胖（内脏脂肪指数<10）分别为440名和581名]。采用甲基化靶向目标区域甲基化测序技术检测JAK2的DNA甲基化水平。使用逻辑回归模型评估JAK2的DNA甲基化水平与肥胖之间的关联。以单核苷酸多态性（SNP）作为工具变量，采用孟德尔随机化分析方法探讨JAK2的DNA甲基化水平与肥胖之间的关联。Chr9:4984943（JAK2启动子中的一个DNA甲基化位点）与肥胖呈正相关，比值比（95%置信区间）为1.22（1.04 - 1.42）。JAK2外显子中五个位点（Chr9:4985378、Chr9:4985404、Chr9:4985407、Chr9:4985409和Chr9:4985435）的甲基化水平与肥胖呈负相关，相应的比值比（95%置信区间）分别为0.53（0.29 - 0.95）、0.58（0.36 - 0.93）、0.69（0.49 - 0.97）、0.72（0.53 - 0.99）和0.58（0.35 - 0.98）。孟德尔随机化分析表明，JAK2的DNA甲基化水平与肥胖之间存在因果关系，对于逆方差加权孟德尔随机化方法、基于中位数的孟德尔随机化方法和最大似然法，相应的因果效应估计值（95%置信区间）分别为-1.985（-3.520 - -0.450）、-3.547（-6.301 - -0.792）和-3.900（-6.328 - -1.472）。本研究支持JAK2的DNA甲基化水平与肥胖之间存在因果关系。
