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

Yongheng Wang,Weiye Qian,Haoyu Sun,Junxi Zhao,Mingdao Mu,Zhiyuan Yang

Published 2025 in Journal of Affective Disorders

ABSTRACT

BACKGROUND The obsessive-compulsive disorder (OCD) is a mental disorder characterized by recurrent, intrusive thoughts and repetitive behaviors. The association between environmental factor and OCD is still not well-studied. 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 some neglected SNPs only indirectly impact OCD 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 pathway of neurodevelopmental disorder. CONCLUSION Our identified environmental factors and SNPs could distinctly promote the understanding and treatment of OCD.

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