Identify key environmental factors and neglected genetic SNPs associated with obsessive-compulsive disorder by two-sample multivariate Mendelian randomization analysis.

Abstract

Background: Obsessive-compulsive disorder (OCD) is a mental disorder characterized by recurrent, intrusive thoughts and repetitive behaviors. The association between environmental factors and OCD remains incompletely understood.

Methods: We applied two-sample multivariate Mendelian randomization analysis by using single nucleotide polymorphisms (SNPs) as instrumental variables to analyze the possible associations between environmental factors and OCD.

Results: Our results showed that depressive symptoms (p-value = 0.0004, OR = 3.234), neuroticism (p-value = 0.0001, OR = 2.502), and educational attainment (p-value = 0.021, OR = 1.467) are significant risk factors for OCD. Conversely, adventurousness (p-value = 0.044, OR = 0.669), eczema (p-value = 0.004, OR = 0.253), and subjective well-being (p-value = 0.002, OR = 0.304) appear to be significant protective factors. In addition, the heterogeneity test for these six environmental factors indicated no significant variations present in this study. The horizontal pleiotropy analysis showed that certain neglected SNPs impact OCD only indirectly through environmental factors, but do not directly influence this disease. By SNP-gene mapping analysis, 11 genes and 11 SNPs were present in those three risk factors. Metabolic pathway analysis showed that these genes were significantly enriched in the pathways of neurodevelopmental disorder.

Conclusion: Our identification of these environmental factors and SNPs significantly advances the understanding of and potential treatments for OCD.