Genetically Determined Risk of Depression and Functional Outcome After Ischemic Stroke: Mendelian Randomization Study
Por:
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, Int Stroke Genetics Consortium, GISCOME Network
Publicada:
1 ago 2019
Resumen:
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 246363 cases and 561190 controls and further replicated in a separate population of 474574 cases and 1032579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60341 cases and 454450 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.
Filiaciones:
Gill, D:
Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England
James, NE:
Imperial Coll London, Fac Med, London, England
Monori, G:
Imperial Coll London, Fac Med, London, England
Lorentzen, E:
Univ Gothenburg, Bioinformat Core Facil, Gothenburg, Sweden
Fernandez-Cadenas, I:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet, Inst Invest Biomed St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Neurol, Neurovasc Res & Alvratory & Neurovasc Unit, Barcelona, Spain
Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Med, Neurovasc Res & Alvratory & Neurovasc Unit, Barcelona, Spain
Lemmens, R:
Univ Leuven, Dept Neurosci, Expt Neurol, Leuven, Belgium
Ctr Brain & Dis Res, Lab Neurobiol, Leuven, Belgium
Univ Hosp Leuven, Dept Neurol, Leuven, Belgium
Thijs, V:
Univ Melbourne, Stroke Div, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia
Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia
Rost, NS:
Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA
Scott, R:
Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW, Australia
Univ Newcastle, Hunter Med Res Inst, Callaghan, NSW, Australia
Hankey, GJ:
Univ Western Australia, Med Sch, Perth, WA, Australia
Lindgren, A:
Skane Univ Hosp, Dept Neurol & Rehabil Med, Neurol, Lund, Sweden
Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden
Jern, C:
Univ Gothenburg Sweden, Sahlgrenska Acad, Dept Clin Pathol & Genet, Inst Biomed, Gothenburg, Sweden
Maguire, JM:
Univ Newcastle, Hunter Med Res Inst, Callaghan, NSW, Australia
Univ Technol Sydney, Fac Hlth, Sydney, NSW, Australia
Univ Newcastle, Prior Res Ctr Stroke & Traumat Brain Injury, Callaghan, NSW, Australia
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