TY - JOUR
T1 - Polygenic risk of ischemic stroke is associated with cognitive ability
AU - Harris, Sarah E.
AU - Malik, Rainer
AU - Marioni, Riccardo
AU - Campbell, Archie
AU - Seshadri, Sudha
AU - Worrall, Bradford B.
AU - Sudlow, Cathie L.M.
AU - Hayward, Caroline
AU - Bastin, Mark E.
AU - Starr, John M.
AU - Porteous, David J.
AU - Wardlaw, Joanna M.
AU - Deary, Ian J.
N1 - Funding Information:
The authors thank all study participants, volunteers, and study personnel who made this consortium possible and the constituent studies for access to their data. LBC1936 and LBC1921: The authors thank the cohort participants who contributed to these studies. GS: The authors are grateful to all the families who took part, the general practitioners, and the Scottish School of Primary Care for their help in recruiting them, and the whole GS team. The METASTROKE Consortium is supported by NINDS (NS017950). See Ref. 12 for detailed funding DISCLOSURE for the METASTROKE Consortium. LBC1936 and LBC1921: Genotyping was supported by the BBSRC. Phenotype collection in LBC1921 was supported by the BBSRC, The Royal Society, and The Chief Scientist Office of the Scottish Government. Phenotype collection in LBC1936 was supported by Research Into Ageing (continues as part of Age UK''s The Disconnected Mind project). Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). S. Harris is supported by the Medical Research Council and the UK''s Biotechnology and Biological Sciences Research Council (BBSRC) (MR/K026992/1). R. Malik is supported by the Vascular Dementia Research Foundation. S. Seshadri is supported by the National Heart, Lung and Blood Institute N01HC2519. R. Marioni and A. Campbell report no disclosures relevant to the manuscript. B. Worrall is supported by the National Institute of Neurological Disorders and Stroke (NINDS) U01NS069208. C. Sudlow is supported by UK Biobank (MRC and Wellcome Trust) and the Scottish Funding Council. C. Hayward and M. Bastin report no disclosures relevant to the manuscript. J. Starr is supported by the Medical Research Council and the UK''s Biotechnology and Biological Sciences Research Council (BBSRC) (MR/K026992/1). D. Porteous and J. Wardlaw report no disclosures relevant to the manuscript. I. Deary is supported by the Medical Research Council and the UK''s Biotechnology and Biological Sciences Research Council (BBSRC) (MR/K026992/1). Go to Neurology.org for full disclosures.
Publisher Copyright:
© 2015 American Academy of Neurology.
PY - 2016/2/16
Y1 - 2016/2/16
N2 - Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Methods: Polygenic risk scores for ischemic stroke were created in LBC1936 (n 1005), LBC1921 (n 517), and GS (n 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. Results: In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r -0.070, p 1.95 × 10 -8). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. Conclusions: The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability.
AB - Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Methods: Polygenic risk scores for ischemic stroke were created in LBC1936 (n 1005), LBC1921 (n 517), and GS (n 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. Results: In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r -0.070, p 1.95 × 10 -8). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. Conclusions: The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability.
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U2 - 10.1212/WNL.0000000000002306
DO - 10.1212/WNL.0000000000002306
M3 - Article
C2 - 26695942
AN - SCOPUS:84959456507
VL - 86
SP - 611
EP - 618
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 7
ER -