Study links psychiatric stress disorders to autoimmune disease at genetic level
Researchers have identified shared genetic pathways between stress-related psychiatric disorders and autoimmune diseases, suggesting the two conditions may stem from common biological roots. The finding could reshape how clinicians diagnose and treat patients with overlapping conditions, and may open new avenues for pharmaceutical intervention in both disease categories.
Originaltitel: Genetic Associations Between Stress-Related Disorders and Autoimmune Disease
<p><strong>Objective</strong>: 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><strong>Methods</strong>: 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><strong>Results</strong>: 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 asso-ciations 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 pheno-types 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><strong>Conclusions</strong>: This study demonstrated familial coaggregation, genetic correlation, and common biological pathways between stress-related disorders and autoimmune disease.</p>