Genetic Susceptibility to Mood Disorders and Risk of Stroke : A Polygenic Risk Score and Mendelian Randomization Study
(2023) In Stroke 54(5). p.1340-1346- Abstract
BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders in stroke.
METHODS: We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and Cancer cohort (24 631 individuals with a median follow-up of 21.3 (interquartile range: 16.6-23.2) years. We further examined the causal effects for mood disorders on all strokes and ischemic strokes using summary statistics from large genome-wide association studies of mood disorders (up to 609 424 individuals, Psychiatric Genomics Consortium), all strokes and ischemic strokes (up to 446 696 individuals, MEGASTROKE... (More)
BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders in stroke.
METHODS: We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and Cancer cohort (24 631 individuals with a median follow-up of 21.3 (interquartile range: 16.6-23.2) years. We further examined the causal effects for mood disorders on all strokes and ischemic strokes using summary statistics from large genome-wide association studies of mood disorders (up to 609 424 individuals, Psychiatric Genomics Consortium), all strokes and ischemic strokes (up to 446 696 individuals, MEGASTROKE Consortium).
RESULTS: Among 24 366 stroke-free participants at baseline, 2632 individuals developed strokes, 2172 of them ischemic, during follow-up. After properly adjusting for well-known risk factors, participants in the highest quintile of polygenic risk scores for mood disorders had 1.45× (95% CI, 1.21-1.74) higher risk of strokes and 1.44× (95% CI, 1.18-1.76) higher risk of ischemic strokes compared with the lowest quintile in women. Mendelian randomization analyses suggested that mood disorders had a causal effect on strokes (odds ratio, 1.07 [95% CI, 1.03-1.11]) and ischemic strokes (odds ratio, 1.09 [95% CI, 1.04-1.13]).
CONCLUSIONS: Our results suggest a causal role of mood disorders in the risk of stroke. High-risk women could be identified early in life using polygenic risk scores to ultimately prevent mood disorders and strokes.
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- author
- Sun, Jiangming LU ; Borné, Yan LU ; Edsfeldt, Andreas LU ; Wang, Yunpeng ; Pan, Mengyu LU ; Melander, Olle LU ; Engström, Gunnar LU and Gonçalves, Isabel LU
- author collaboration
- organization
-
- Cardiovascular Research - Translational Studies (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Nutrition Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- WCMM-Wallenberg Centre for Molecular Medicine
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Cardiovascular Research - Hypertension (research group)
- Cardiovascular Research - Epidemiology (research group)
- publishing date
- 2023-05
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Stroke
- volume
- 54
- issue
- 5
- pages
- 1340 - 1346
- publisher
- American Heart Association
- external identifiers
-
- pmid:36942587
- scopus:85153804494
- ISSN
- 1524-4628
- DOI
- 10.1161/STROKEAHA.122.041026
- language
- English
- LU publication?
- yes
- id
- c2df21cd-0fd8-49d8-9dac-bdc2f9fbe854
- date added to LUP
- 2023-03-25 10:30:03
- date last changed
- 2024-07-30 08:46:05
@article{c2df21cd-0fd8-49d8-9dac-bdc2f9fbe854, abstract = {{<p>BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders in stroke.</p><p>METHODS: We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and Cancer cohort (24 631 individuals with a median follow-up of 21.3 (interquartile range: 16.6-23.2) years. We further examined the causal effects for mood disorders on all strokes and ischemic strokes using summary statistics from large genome-wide association studies of mood disorders (up to 609 424 individuals, Psychiatric Genomics Consortium), all strokes and ischemic strokes (up to 446 696 individuals, MEGASTROKE Consortium).</p><p>RESULTS: Among 24 366 stroke-free participants at baseline, 2632 individuals developed strokes, 2172 of them ischemic, during follow-up. After properly adjusting for well-known risk factors, participants in the highest quintile of polygenic risk scores for mood disorders had 1.45× (95% CI, 1.21-1.74) higher risk of strokes and 1.44× (95% CI, 1.18-1.76) higher risk of ischemic strokes compared with the lowest quintile in women. Mendelian randomization analyses suggested that mood disorders had a causal effect on strokes (odds ratio, 1.07 [95% CI, 1.03-1.11]) and ischemic strokes (odds ratio, 1.09 [95% CI, 1.04-1.13]).</p><p>CONCLUSIONS: Our results suggest a causal role of mood disorders in the risk of stroke. High-risk women could be identified early in life using polygenic risk scores to ultimately prevent mood disorders and strokes.</p>}}, author = {{Sun, Jiangming and Borné, Yan and Edsfeldt, Andreas and Wang, Yunpeng and Pan, Mengyu and Melander, Olle and Engström, Gunnar and Gonçalves, Isabel}}, issn = {{1524-4628}}, language = {{eng}}, number = {{5}}, pages = {{1340--1346}}, publisher = {{American Heart Association}}, series = {{Stroke}}, title = {{Genetic Susceptibility to Mood Disorders and Risk of Stroke : A Polygenic Risk Score and Mendelian Randomization Study}}, url = {{http://dx.doi.org/10.1161/STROKEAHA.122.041026}}, doi = {{10.1161/STROKEAHA.122.041026}}, volume = {{54}}, year = {{2023}}, }