Genetically Determined Risk of Depression and Functional Outcome after Ischemic Stroke: Mendelian Randomization Study

Gill, D; James, NE; Monori, G; Lorentzen, E; Fernandez-Cadenas, I; Lemmens, R; Thijs, V; Rost, NS; Scott, R; Hankey, GJ; Lindgren, A; Jern, C; Maguire, JM

Genetically Determined Risk of Depression and Functional Outcome after Ischemic Stroke: Mendelian Randomization Study

Gill, D James, NE Monori, G Lorentzen, E Fernandez-Cadenas, I Lemmens, R Thijs, V Rost, NS Scott, R Hankey, GJ Lindgren, A Jern, C Maguire, JM

Permalink

Publication Type:: Journal Article
Citation:: Stroke, 2019, 50 (8), pp. 2219 - 2222
Issue Date:: 2019-08-01

Closed Access

	Filename	Description	Size
	00007670-201908000-00045.pdf	Published Version	130.67 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Gill, D	en_US
dc.contributor.author	James, NE	en_US
dc.contributor.author	Monori, G	en_US
dc.contributor.author	Lorentzen, E	en_US
dc.contributor.author	Fernandez-Cadenas, I	en_US
dc.contributor.author	Lemmens, R	en_US
dc.contributor.author	Thijs, V	en_US
dc.contributor.author	Rost, NS	en_US
dc.contributor.author	Scott, R	en_US
dc.contributor.author	Hankey, GJ	en_US
dc.contributor.author	Lindgren, A	en_US
dc.contributor.author	Jern, C	en_US
dc.contributor.author	Maguire, JM https://orcid.org/0000-0001-5722-8311	en_US
dc.date.issued	2019-08-01	en_US
dc.identifier.citation	Stroke, 2019, 50 (8), pp. 2219 - 2222	en_US
dc.identifier.issn	0039-2499	en_US
dc.identifier.uri	http://hdl.handle.net/10453/135690
dc.description.abstract	© 2019 American Heart Association, Inc. 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.	en_US
dc.relation.ispartof	Stroke	en_US
dc.relation.isbasedon	10.1161/STROKEAHA.119.026089	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.title	Genetically Determined Risk of Depression and Functional Outcome after Ischemic Stroke: Mendelian Randomization Study	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	50	en_US
utslib.for	1117 Public Health and Health Services	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Nursing
utslib.copyright.status	closed_access	*
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	50	en_US

Abstract:

© 2019 American Heart Association, Inc. 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/135690