Advanced

Genetically Determined Risk of Depression and Functional Outcome After Ischemic Stroke

Gill, Dipender ; James, Nicole E. ; Monori, Grace ; Lorentzen, Erik ; Fernandez-Cadenas, Israel ; Lemmens, Robin ; Thijs, Vincent ; Rost, Natalia S. ; Scott, Rodney and Hankey, Graeme J. , et al. (2019) In Stroke 50(8). p.2219-2222
Abstract

Background and Purpose- Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods- Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical... (More)

Background and Purpose- Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods- Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. Results- There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81; 95% CI, 0.98-3.35; P=0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P=0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57; 95% CI, 1.05-6.25; P=0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81; 95% CI, 0.95-3.46; P=0.08). Conclusions- We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
depression, morbidity, stroke
in
Stroke
volume
50
issue
8
pages
4 pages
publisher
American Heart Association
external identifiers
  • scopus:85070183371
  • pmid:31238828
ISSN
1524-4628
DOI
10.1161/STROKEAHA.119.026089
language
English
LU publication?
yes
id
8eb390b6-4564-4680-8484-e64c80a07e15
date added to LUP
2019-08-29 09:21:18
date last changed
2020-01-16 04:04:11
@article{8eb390b6-4564-4680-8484-e64c80a07e15,
  abstract     = {<p>Background and Purpose- Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods- Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. Results- There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81; 95% CI, 0.98-3.35; P=0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P=0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57; 95% CI, 1.05-6.25; P=0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81; 95% CI, 0.95-3.46; P=0.08). Conclusions- We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.</p>},
  author       = {Gill, Dipender and James, Nicole E. and Monori, Grace and Lorentzen, Erik and Fernandez-Cadenas, Israel and Lemmens, Robin and Thijs, Vincent and Rost, Natalia S. and Scott, Rodney and Hankey, Graeme J. and Lindgren, Arne and Jern, Christina and Maguire, Jane M.},
  issn         = {1524-4628},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {2219--2222},
  publisher    = {American Heart Association},
  series       = {Stroke},
  title        = {Genetically Determined Risk of Depression and Functional Outcome After Ischemic Stroke},
  url          = {http://dx.doi.org/10.1161/STROKEAHA.119.026089},
  doi          = {10.1161/STROKEAHA.119.026089},
  volume       = {50},
  year         = {2019},
}