Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China; Department of Clinical Pharmacology, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, PR China.
Nutr Metab Cardiovasc Dis. 2021 Nov 29;31(12):3484-3491. doi: 10.1016/j.numecd.2021.08.046. Epub 2021 Sep 6.
Janus kinase 2 (JAK2) play an important role in the energy metabolism. Whether there is a causal relationship between JAK2 methylation levels and obesity remains unclear. Based on the instrumental variables of 5 SNP sites, this study was aimed to explore the causal relationship between JAK2 methylation levels and obesity by Mendelian randomization analysis.
A total of 1021 participants (511 cases and 510 controls defined by body mass index (BMI) ≥ 28.0 kg/m) was conducted from the Henan Rural Cohort study. SNPscan® was performed to test the SNP genotyping and MethylTarget™ was applied to detect the DNA methylation level. The logistic regression model was used to evaluate the associations between SNP or methylation of JAK2 and obesity (according to BMI). Mendelian randomization analysis was used to assess the potential causal association between JAK2 methylation and obesity. According to the logistic regression model, 1 CpG sit in the promotor was related to an increased risk of obesity (P < 0.05). 10 CpG sites in the exon were associated with decreased risk of obesity (P < 0.05). Mendelian randomization analysis showed a causal association between the methylated level of JAK2 and obesity, based on the instrumental variables of 5 SNPs (P < 0.05).
This study supported that the methylation degree of JAK2 has a complex relationship with obesity, which might be related to the region of methylation. A causal relationship exists between the methylated level of JAK2 and obesity.
Janus 激酶 2（JAK2）在能量代谢中发挥重要作用。JAK2 甲基化水平与肥胖之间是否存在因果关系尚不清楚。本研究基于 5 个 SNP 位点的工具变量，通过孟德尔随机化分析探讨 JAK2 甲基化水平与肥胖之间的因果关系。
本研究共纳入 1021 名参与者（根据体重指数（BMI）≥28.0 kg/m 定义的 511 例病例和 510 例对照），来自河南农村队列研究。采用 SNPscan®检测 SNP 基因分型，MethylTarget™检测 DNA 甲基化水平。采用 logistic 回归模型评估 SNP 或 JAK2 甲基化与肥胖（根据 BMI）之间的关联。采用孟德尔随机化分析评估 JAK2 甲基化与肥胖之间的潜在因果关系。根据 logistic 回归模型，启动子中的 1 个 CpG 位点与肥胖风险增加相关（P<0.05）。外显子中的 10 个 CpG 位点与肥胖风险降低相关（P<0.05）。基于 5 个 SNP 的工具变量，孟德尔随机化分析显示 JAK2 甲基化水平与肥胖之间存在因果关系（P<0.05）。
本研究支持 JAK2 甲基化程度与肥胖之间存在复杂关系，可能与甲基化区域有关。JAK2 甲基化水平与肥胖之间存在因果关系。
