Stress-related disorders genetically linked to autoimmune disease

Genetic associations, as well as familial coaggregation and common biological pathways, exist between stress-related disorders and autoimmune disease, a recent study has shown.

The authors used data from 4,123,631 individuals identified from Swedish nationwide registers to initially estimate familial coaggregation of stress-related disorders (any disorder or post-traumatic stress disorder [PTSD]) and autoimmune disease in seven cohorts with different degrees of kinship.

Then, they conducted analyses of polygenic risk score (PRS) with individual-level genotyping data from 376,871 participants in the UK Biobank study. Genome-wide association study (GWAS) summary statistics were used to perform genetic correlation and enrichment analyses.

In familial coaggregation analyses, the likelihood of concurrence of stress-related disorders and autoimmune disease decreased with descending kinship or genetic relatedness between pairs of relatives. The adjusted odds ratios were 1.51 (95 percent confidence interval [CI], 1.09‒2.07) for monozygotic twins, 1.28 (95 percent CI, 0.97‒1.68) for dizygotic twins, 1.16 (95 percent CI, 1.14‒1.18) for full siblings, and 1.01 (95 percent CI, 0.98‒1.03) for half cousins.

The PRS of stress-related disorders significantly correlated with autoimmune disease, as did the PRS of autoimmune disease and stress-related disorders. GWAS summary statistics showed a genetic association of 0.26 (95 percent CI, 0.14‒0.38) between these phenotypes and revealed 10 common genes and five shared functional models, including one related to G-protein‒coupled receptor pathways.

“Similar analyses performed for PTSD and specific autoimmune diseases (eg, autoimmune thyroid disease) largely recapitulated the results of the main analyses,” the authors said.