Polygenic risk scores for mood disorders predict future strokes in women: a Mendelian randomization study

Abstract Objectives Mood disorders and strokes are often comorbid, their health toll worldwide is huge. This study characterizes prognostic etiological roles of mood in stroke. Methods We tested if genetic susceptibilities for could predict future using the Malmö Diet Cancer cohort (24 631 individuals). Additionally, Mendelian randomization was employed to further examine causality summary statistics from large genome wide association studies (mood disorders: up 287,932 individuals; strokes: 446,696 Results Among 24,366 stroke-free participants at baseline, 2,632 individuals developed strokes, 2,172 them ischemic, during a follow-up 25 years. After all adjustments, highest quintile (5th quintile) polygenic risk scores (PRS) had 1.46x (95% confidence interval (CI): 1.22–1.74) higher 1.45x CI: 1.19–1.77) ischemic compared lowest (1st PRS women. Univariable multivariable analyses showed that causal effect on smoking (odds ratio (OR) = 1.19, 95% 1.07–1.31), type 2 diabetes mellitus (T2D, OR=1.22, 1.04–1.43) women's body mass index (BMI, coefficient 0.11, 0.01–0.21), whereas effects smoking, T2D BMI stroke/ischemic stroke were consistently observed. Conclusion Our results suggest can cause through BMI. Using PRS, women, who benefit prevention treatment BMI, possibly be early identified prevent strokes. Funding Acknowledgement Type funding sources: Other. Main source(s): Swedish Research Council, Heart Lung Foundation, Skåne University Hospital Foundations, Lund Diabetes Center - Industrial Foundation Strategic Research, Region Grants, Stroke society medicine, Söderström König Emil Wera Cornell Hjelt Wellness Sweden.