文章摘要
刘晓田,屠润琪,何亚玲,董小康,李瑞颖,侯建,李玉倩,王重建.JAK2基因甲基化与肥胖因果关联的孟德尔随机化研究[J].中华流行病学杂志,2022,43(8):1315-1320
JAK2基因甲基化与肥胖因果关联的孟德尔随机化研究
Mendelian randomization analysis: the causal relationship between the DNA methylation levels of JAK2 and obesity
收稿日期:2022-03-18  出版日期:2022-08-13
DOI:10.3760/cma.j.cn112338-20220318-00200
中文关键词: 肥胖  酪氨酸激酶2  DNA甲基化  孟德尔随机化
英文关键词: Obesity  Janus kinase 2  DNA methylation  Mendelian randomization analysis
基金项目:国家重点研发计划(2016YFC0900803);国家自然科学基金(82003543);河南省高校科技创新团队项目(21IRTSTHN029)
作者单位E-mail
刘晓田 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
屠润琪 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
何亚玲 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
董小康 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
李瑞颖 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
侯建 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
李玉倩 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001  
王重建 郑州大学公共卫生学院流行病与卫生统计学系, 郑州 450001 tjwcj2008@zzu.edu.cn 
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中文摘要:
      目的 采用孟德尔随机化法探讨酪氨酸激酶2(JAK2)基因甲基化水平与肥胖的因果关联。方法 从河南农村队列中选取1 021例研究对象,其中440例肥胖者(内脏脂肪指数≥10)和581例对照者(内脏脂肪指数<10)。采用MethylTargetTM目标区域甲基化测序技术检测JAK2基因甲基化水平;采用logistic回归模型分析JAK2基因甲基化水平与肥胖的关联;进一步以单核苷酸多态性为工具变量,采用孟德尔随机化法分析JAK2基因甲基化水平与肥胖的因果关联。结果 JAK2基因的启动子区发现1个甲基化位点(Chr9:4984943)与肥胖呈正相关(OR=1.22,95%CI:1.04~1.42)。外显子区发现5个甲基化位点(Chr9:4985378、Chr9:4985404、Chr9:4985407、Chr9:4985409和Chr9:4985435)与肥胖呈负相关[OR值(95%CI)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)]。3种孟德尔随机化法(逆方差加权孟德尔随机化法、基于中位数孟德尔随机化法和最大似然比法)的结果均显示JAK2基因甲基化水平与肥胖存在因果关联,其相应的β值(95%CI)分别为-1.985(-3.520~-0.450)、-3.547(-6.301~-0.792)和-3.900(-6.328~-1.472)。结论 JAK2基因甲基化水平与肥胖存在因果关联。
英文摘要:
      Objective Based on the Mendelian randomization analysis, to assess the causal relationship between DNA methylation levels of Janus kinase 2 (JAK2) and obesity. Methods A case-control study was carried out, including 1 021 individuals[obesity (visceral fat index ≥ 10) vs. no obesity (visceral fat index <10) was 440 vs. 581] from the Henan Rural Cohort Study. MethylTargetTM 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. Results There was a positive association between Chr9:4984943 (one DNA methylation site in the promoter of JAK2) and obesity, and the OR (95%CI) 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 OR (95%CI) 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 β (95%CI) 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. Conclusion This study supported there was a causal relationship between the DNA methylation level of JAK2 and obesity.
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