Polygenic Risk for Depression is Associated with Post-Stroke Depression and Stroke

Abstract Background Depression is a highly heritable mental health condition. However, the role of genetic susceptibility to depression in post-stroke depression (PSD) and the pathway from stroke to PSD have not yet been thoroughly studied. Methods We conducted a case-control genetic association study by using clinical data from the UK Biobank. The exposure of interest was the polygenic risk score for depression, modeled in deciles for logistic regression analysis and in tertiles for survival regression analysis. All models have been adjusted for age, sex, and the first five principal genetic components. Result Among the 11,130 stroke patients in UK Biobank who had complete genetic information, 584 were diagnosed with depression for the first time after the stroke, of which 196 were diagnosed with depression for the first time within one year after the stroke. Multivariable logistic regression analysis revealed that participants in the highest decile of the depression PRS had higher risk of developing PSD compared to that in the lowest decile (OR = 3.32, 95% CI: 2.32–4.87, P < 0.001).When restricting the outcome to incident depression occurring within 1 year after stroke, participants in the highest PRS decile had 11-fold higher odds of post-stroke depression (PSD) than those in the lowest decile (OR 11.39, 95% CI 9.15–14.31; p<0.001). Similarly, for the high PRS group, the risk of stroke also significantly increases. Conclusion Our findings indicate that genetic factors play a crucial role in the pathogenesis of PSD, and that the polygenic susceptibility to depression is associated with both stroke and the risk of developing PSD.