| Title: | Genetic Associations Between Stress-Related Disorders and Autoimmune Disease |
| Journal: | American Journal of Psychiatry |
| Published: | 27 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37002690/ |
| DOI: | https://doi.org/10.1176/appi.ajp.20220364 |
Publication 11238
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Abstract
Objective:</p>
Emerging evidence supports a bidirectional phenotypic association between stress-related disorders and autoimmune disease. However, the biological underpinnings remain unclear. Here, the authors examined whether and how shared genetics contribute to the observed phenotypic associations.</p>
</p>
Methods:</p>
Based on data from 4,123,631 individuals identified from Swedish nationwide registers, familial coaggregation of stress-related disorders (any disorder or posttraumatic stress disorder [PTSD]) and autoimmune disease were initially estimated in seven cohorts with different degrees of kinship. Polygenic risk score (PRS) analyses were then performed with individual-level genotyping data from 376,871 participants in the UK Biobank study. Finally, genetic correlation analyses and enrichment analyses were performed with genome-wide association study (GWAS) summary statistics.</p>
</p>
Results:</p>
Familial coaggregation analyses revealed decreasing odds of concurrence of stress-related disorders and autoimmune disease with descending kinship or genetic relatedness between pairs of relatives; adjusted odds ratios were 1.51 (95% CI=1.09-2.07), 1.28 (95% CI=0.97-1.68), 1.16 (95% CI=1.14-1.18), and 1.01 (95% CI=0.98-1.03) for monozygotic twins, dizygotic twins, full siblings, and half cousins, respectively. Statistically significant positive associations were observed between PRSs of stress-related disorders and autoimmune disease, as well as between PRSs of autoimmune disease and stress-related disorders. GWAS summary statistics revealed a genetic correlation of 0.26 (95% CI=0.14-0.38) between these two phenotypes and identified 10 common genes and five shared functional modules, including one module related to G-protein-coupled receptor pathways. Similar analyses performed for PTSD and specific autoimmune diseases (e.g., autoimmune thyroid disease) largely recapitulated the results of the main analyses.</p>
</p>
Conclusions:</p>
This study demonstrated familial coaggregation, genetic correlation, and common biological pathways between stress-related disorders and autoimmune disease.</p>
10 Authors
- Yu Zeng
- Chen Suo
- Shuyang Yao
- Donghao Lu
- Henrik Larsson
- Brian M D'Onofrio
- Paul Lichtenstein
- Fang Fang
- Unnur A Valdimarsdóttir
- Huan Song
1 Application
| Application ID | Title |
|---|---|
| 54803 | Deciphering complex traits - phenotypic and genetic associations between traits in the UK Biobank Cohort |
Enabling scientific discoveries that improve human health