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Genome-Wide Analyses Reveal Shared Genetic Architecture and Potential Causal Relationships between Osteoarthritis and Psychiatric Disorders
326 Pages Posted: 14 May 2024
More...Abstract
Background: Osteoarthritis (OA) and psychiatric disorders are prevalent conditions that frequently co-occur, suggesting potential shared genetic underpinnings. However, the extent of genetic correlations and causal relationships between these disorders remains largely unknown.
Methods: We performed cross-trait genetic correlation analyses using genome-wide association study (GWAS) summary statistics for OA and eight psychiatric disorders. We identified shared risk loci and genes through pleiotropy analysis and functional annotation. Bidirectional Mendelian randomization was employed to investigate causal relationships between OA and psychiatric disorders.
Findings: Significant genetic correlations were observed between OA and several psychiatric disorders, particularly attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ). We identified 188 pleiotropic loci and 511 shared genes, with functional enrichment in brain tissues, inflammatory pathways, and immune cell types. Mendelian randomization analyses indicated potential causal effects of ADHD and MDD on knee OA, as well as bidirectional causal relationships between OA and Alzheimer's disease.
Interpretation: Our findings revealed a shared genetic architecture between OA and psychiatric disorders, providing novel insights into their comorbidity. The identified pleiotropic loci, shared genes, and biological pathways offer potential targets for further research and drug development. The causal relationships suggest that targeting psychiatric disorders may have implications for OA prevention and treatment.
Funding: None.
Declaration of Interest: The authors declare that they have no competing interests.
Ethical Approval: All GWAS were approved by relevant ethic committees, and written informed consent was obtained from all participants.
Keywords: Osteoarthritis, Psychiatric disorders, Genome-wide association study (GWAS), Pleiotropy, Mendelian randomization
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