Exploring the association of age at first sexual intercourse and lifetime number of sexual partners on neurological and psychiatric disorders: An observational and genetic study.

BACKGROUND AND

OBJECTIVES

Emerging evidence suggests that sexual behaviors play a critical but understudied role in neurological and psychiatric health. The causal and biological mechanisms linking age at first sexual intercourse (AFS) and lifetime number of sexual partners (LNSP) to brain disorders remain unknown. This study aims to determine whether sexual behavior influences neurological and psychiatric disorders through biological mechanisms, integrating observational and genetic evidence to uncover causal pathways.

METHODS

Utilizing data from the UK Biobank, the relationships of AFS and LNSP with neurological and psychiatric disorders, brain structure, and inflammation indicators were examined with Cox proportional hazards and linear regression model and further examined the potential causality, genetic correlation, and shared genetics by Mendelian randomization, linkage disequilibrium score regression, multi-trait analysis of genome-wide association studies, transcriptome-wide association studies, and functional enrichment analysis.

RESULTS

In this large-scale study of 394,395 participants with a median follow-up of 14.7 years, earlier AFS and higher LNSP were associated with increased risks of stroke, major depressive disorder, anxiety disorders, and bipolar disorder. These behavioral traits were also linked to alterations in gray/white matter and inflammatory markers. Mendelian randomization and linkage disequilibrium score regression analyses confirmed causal relationships and shared heritability with brain disorders, multi-trait analysis of genome-wide association studies and transcriptome-wide association studies, revealing overlapping genetic influences in blood and neural tissues. Functional enrichment analysis demonstrated shared biological pathways including immunity.

CONCLUSIONS

This study provides robust evidence linking sexual behavior traits to neurological and psychiatric disorders through large-scale longitudinal analyses, causal genetic methods, and multi-omics integration.