| Xu Jiaqing,Xu Chen,Gu Xiaochu,Pang Lijun,Shen Jing,Ye Liya,Shared genetic architecture between arrhythmia and obsessive-compulsive disorder： a heart-brain axis study based on multi-omics integration[J].SICHUAN MENTAL HEALTH,2026,(2):149-157 |
| Shared genetic architecture between arrhythmia and obsessive-compulsive disorder： a heart-brain axis study based on multi-omics integration |
DOI：10.11886/scjsws20260115001 |
| English keywords:Arrhythmia Obsessive-compulsive disorder Genetic correlation Pleiotropy Heart-brain axis Multi-omics integration |
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| Author Name | Affiliation | Postcode | | Xu Jiaqing | 1The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou 215200, China | 215200 | | Xu Chen | 2Suzhou Ninth People's Hospital Affiliated to Soochow University, Suzhou 215200, China | 215200 | | Gu Xiaochu | 3Guangji Hospital Affiliated to Soochow University, Suzhou 215137, China | 215137 | | Pang Lijun | 1The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou 215200, China | 215200 | | Shen Jing | 1The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou 215200, China | 215200 | | Ye Liya* | 1The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou 215200, China | 215200 |
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| Background Arrhythmia and obsessive-compulsive disorder （OCD） frequently co-occur in clinical and epidemiological settings， yet their shared genetic basis and potential heart-brain axis mechanisms remain unclear.Objective To systematically evaluate the genetic correlation between arrhythmia and OCD， and to elucidate their underlying molecular genetic mechanisms， so as to provide molecular evidence for the "heart-brain axis" to support risk assessment and integrated clinical strategies for these comorbidities.Methods The aggregated data from the genome-wide association study （GWAS） of arrhythmia in the UK Biobank （7 207 cases and 477 391 controls） and the GWAS data of OCD released by the Psychiatric Genomics Consortium （2 688 cases and 7 037 controls） were integrated， all of which were limited to individuals of European ancestry. The genome-wide genetic correlations were estimated using the linkage disequilibrium score regression （LDSC） and the high-definition likelihood （HDL）. Local genetic correlation analysis was conducted using the local analysis of variance annotation （LAVA）. Multi-trait analysis of GWAS （MTAG） was employed to identify pleiotropic loci. Shared risk genes were identified by combining summary-data based Mendelian randomization （SMR） and transcriptome-wide association study （TWAS）. Functional enrichment analysis was performed based on the functional mapping and annotation （FUMA） platform.Results Both LDSC （rg=0.248， 95% CI： 0.159–0.336， P=4.82×10-3） and HDL （rg=0.294， 95% CI： 0.237–0.351， P=5.87×10-4） revealed significant positive genetic correlation between arrhythmia and OCD. LAVA identified 23 significantly local correlated regions in the genome （P<2.0×10-5）. MTAG discovered 11 genome-wide significant pleiotropic SNPs， among which rs12754189 （intron of KCNN3） had potential functional harmfulness （CADD>12.37）. SMR and TWAS jointly identified 20 shared genes， enriched in neural-cardiovascular tissues such as the cerebral cortex， amygdala， and left ventricle， and involved in DNA damage response， RNA metabolism， transcriptional regulation， and FAS signaling pathway （FDR<0.05）.Conclusion Arrhythmia and OCD share a common genetic basis. The co-morbidity mechanism may involve the common vulnerability of neurons and cardiac muscle cells in terms of gene expression regulation and stress response， supporting the role of the brain-heart axis in the pathophysiology of both conditions. |
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