Janus kinase 2 (JAK2) methylation and obesity: A Mendelian randomization study.

BACKGROUND AND AIMS

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.

METHODS AND RESULTS

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).

CONCLUSIONS

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.