Mendelian Randomization Analysis of the Association of SOCS3 Methylation with Abdominal Obesity

This study was conducted to evaluate the potential causality association of SOCS3 methylation with abdominal obesity using Mendelian randomization. A case-control study, including 1064 participants, was carried out on Chinese subjects aged 18 to 79. MethylTargetTM was used to detect the methylation level for each CpG site of SOCS3, and SNPscan^® was applied to measure the single-nucleotide polymorphism (SNP) genotyping. The logistic regression was used to assess the relationship of SOCS3 methylation level and SNP genotyping with abdominal obesity. Three types of Mendelian randomization methods were implemented to examine the potential causality between SOCS3 methylation and obesity based on the SNP of SOCS3 as instrumental variables. SOCS3 methylation levels were inversely associated with abdominal obesity in five CpG sites (effect estimates ranged from 0.786 (Chr17:76356054) to 0.851 (Chr17:76356084)), and demonstrated positively association in 18 CpG sites (effect estimates ranged from 1.243 (Chr17:76354990) to 1.325 (Chr17:76355061)). The causal relationship between SOCS3 methylation and abdominal obesity was found using the maximum-likelihood method and Mendelian randomization method of penalized inverse variance weighted (MR-IVW), and the β values (95% CI) were 5.342 (0.215, 10.469) and 4.911 (0.259, 9.564), respectively. The causality was found between the SOCS3 methylation level and abdominal obesity in the Chinese population.