Epigenetic Mechanisms Regulating the Association betweenOR2L13and Major Psychiatric Disorders

Background Previously, population-based cohort studies have identified the association between epigenetic modifications of OR2L13 related to mental disorders and Gestational diabetes mellitus (GDM). However, the causal nature of these associations remains difficult to establish owing to confounding. Aims The purpose of the study was to investigate the causal effect of methylation of OR2L13 and offspring mental health outcomes. Method We performed two-sample mendelian randomisation to assess the effect of methylation of OR2L13 on mental disorders. Methylation of 7 CpG sites within OR2L13 related to GDM from two previous studies were used as exposure. Genome wide significant single nucleotide polymorphisms for methylation of OR2L13 retrieved from published data were used as instrumental variables. Their causal impact on major psychiatric disorders was assessed using summary-level data mostly from the Psychiatric Genomics Consortium. Results Lower OR2L13 methylation was casually associated with a higher risk of PD in offspring [cg03748376: odds ratio (OR)=0.81, 95% confidence interval (CI) =0.68–0.97, P =0.02]. However, little evidence was found for a causal relationship between the methylation levels of OR2L13 and autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), bipolar disorder (BD) and obsessive-compulsive disorder (OCD). Conclusions Evidence from our study supported a causal effect of lower OR2L13 methylation on PD risk.