Genetic Susceptibility to Mood Disorders and Risk of Stroke: A Polygenic Risk Score and Mendelian Randomization Study

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. We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and...

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Published inStroke (1970) Vol. 54; no. 5; pp. 1340 - 1346
Main Authors Sun, Jiangming, Borné, Yan, Edsfeldt, Andreas, Wang, Yunpeng, Pan, Mengyu, Melander, Olle, Engström, Gunnar, Gonçalves, Isabel
Format Journal Article
LanguageEnglish
Published United States Lippincott Williams & Wilkins 01.05.2023
Subjects
Clinical Medicine
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Ischemic Stroke
Klinisk medicin
Medical and Health Sciences
Medicin och hälsovetenskap
Mendelian Randomization Analysis
Mood Disorders
Neurologi
Neurology
Polymorphism, Single Nucleotide
Risk Factors
Stroke - genetics
cardiovascular disease
prevalence
mental illness
patient
population
Online AccessGet full text
ISSN0039-2499
1524-4628
1524-4628
DOI10.1161/STROKEAHA.122.041026

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Abstract 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. 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). 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]). 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.
AbstractList 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. 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). 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]). 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.
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.BACKGROUNDMood 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.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).METHODSWe 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).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]).RESULTSAmong 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]).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.CONCLUSIONSOur 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.
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.
Author Borné, Yan
Gonçalves, Isabel
Edsfeldt, Andreas
Pan, Mengyu
Engström, Gunnar
Wang, Yunpeng
Sun, Jiangming
Melander, Olle
AuthorAffiliation Lifespan Changes in Bain and Cognition (LCBC), Department of Psychology, University of Oslo, Norway (Y.W., M.P.). Regeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden (J.S., Y.B., A.E., M.P., O.M., G.E., I.G.)
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36942587$$D View this record in MEDLINE/PubMed
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crossref_primary_10_1016_j_jad_2024_03_076
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Keywords cardiovascular disease
prevalence
mental illness
patient
population
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PublicationTitle Stroke (1970)
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Snippet Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders...
BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of...
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SubjectTerms Clinical Medicine
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Ischemic Stroke
Klinisk medicin
Medical and Health Sciences
Medicin och hälsovetenskap
Mendelian Randomization Analysis
Mood Disorders
Neurologi
Neurology
Polymorphism, Single Nucleotide
Risk Factors
Stroke - genetics
Title Genetic Susceptibility to Mood Disorders and Risk of Stroke: A Polygenic Risk Score and Mendelian Randomization Study
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https://www.ncbi.nlm.nih.gov/pubmed/36942587
https://www.proquest.com/docview/2789234963
Volume 54
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