Integrative analysis of genome-wide association study and common meQTLs for exploring the effects of DNA methylation on the development of neuroticism

Abstract Background Neuroticism is one of the important traits of personality, which has strong genetic components. However, the underlying genetic mechanism is still unclear. Methods To better understand the genetic basis of neuroticism, we conducted an integrative analysis of genome-wide association studies (GWAS) and life course consistent methylation quantitative trait loci (meQTLs) data. The GWAS data of neuroticism was derived from a published study of neuroticism (including 170,906 subjects). Life course consistent meQTLs were obtained from a large scale longitudinal meQTLs analysis (including 1,018 mother–child pairs).Gene prioritization, pathway and tissue/cell type enrichment analyses were implemented by DEPICT. Results We identified multiple genes, pathways and tissues associated with neuroticism, such as NEIL2 (P value = 1.31 × 10−2), ARHGAP27 (P value = 1.40 × 10−2), REACTOME_CLATHRIN_DERIVED_VESICLE_BUDDING(P value =4.92 × 10−6) ,REACTOME_TRANS:GOLGI_NETWORK_VESICLE_BUDDING (P value =4.92 × 10−6), frontal lobe(P value =3.83 × 10−3) and visual cortex (P value =8.46 × 10−3). Conclusions Our results provide novel insights for understanding the genetic mechanism of neuroticism.