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A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort

Lookup NU author(s): Olivia Skrobot, Professor Raj KalariaORCiD, Dr Timo Erkinjuntti

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Abstract

Vascular cognitive impairment (VCI), including its severe form, vascular dementia (VaD), is the second most common form of dementia. The genetic etiology of sporadic VCI remains largely unknown. We previously conducted a systematic review and meta-analysis of all published genetic association studies of sporadic VCI prior to 6 July 2012, which demonstrated that APOE (epsilon 4, epsilon 2) and MTHFR (rs1801133) variants were associated with susceptibility for VCI. De novo genotyping was conducted in a new independent relatively large collaborative European cohort of VaD (n(max) = 549) and elderly non-demented samples (n(max) = 552). Where available, genotype data derived from Illumina's 610-quad array for 1210 GERAD1 control samples were also included in analyses of genes examined. Associations were tested using the Cochran-Armitage trend test: MTHFR rs1801133 (OR = 1.36, 95% CI 1.16-1.58, p = < 0.0001), APOE rs7412 (OR = 0.62, 95% CI 0.42-0.90, p = 0.01), and APOE rs429358 (OR = 1.59, 95% CI 1.17-2.16, p = 0.003). Association was also observed with APOE epsilon alleles; epsilon 4 (OR = 1.85, 95% CI 1.35-2.52, p = < 0.0001) and epsilon 2 (OR = 0.67, 95% CI 0.46-0.98, p = 0.03). Logistic regression and Bonferroni correction in a subgroup of the cohort adjusted for gender, age, and population maintained the association of APOE rs429358 and epsilon 4 allele.


Publication metadata

Author(s): Skrobot OA, McKnight AJ, Passmore PA, Seripa D, Mecocci P, Panza F, Kalaria R, Wilcock G, Munafo M, Erkinjuntti T, Karhunen P, Pessi T, Martiskainen M, Love S, Kehoe PG, Genetic Environm Risk Alzheimer's

Publication type: Article

Publication status: Published

Journal: Journal of Alzheimer's Disease

Year: 2016

Volume: 53

Issue: 3

Pages: 981-989

Online publication date: 03/08/2016

Acceptance date: 25/04/2016

ISSN (print): 1387-2877

ISSN (electronic): 1875-8908

Publisher: IOS Press

URL: http://dx.doi.org/10.3233/JAD-150862

DOI: 10.3233/JAD-150862


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Funding

Funder referenceFunder name
Alfried Krupp von Bohlen und Halbach-Stiftung
Alzheimer's Research UK (ARUK)
Alzheimer's Society
ARUK as part of the Brains for Dementia Research Project
BRACE (Bristol Research into Alzheimer's and Care of the Elderly)
Brains for Dementia Research
Bristol Research into Alzheimer's care of the Elderly
German Federal Ministry of Education and Research (BMBF), Competence Network Dementia
Lundbeck SA
MRC
N. Ireland RD Office
Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases
NIH
Wellcome Trust
Welsh Assembly Government
Barnes Jewish Foundation
Charles and Joanne Knight Alzheimer's Research Initiative
Charles Wolfson Charitable Trust
German Federal Ministry of Education and Research (BMBF), Competence Network Degenerative Dementia
Medical Research Council
Mercer's Institute for Research on Ageing
NIHR Biomedical Research Centre Programme, Oxford
Royal College of Physicians/Dunhill Medical Trust
Sigmund Gestetner Foundation
UCLH/UCL Biomedical Centre
Ulster Garden Villages
G0400074UK MRC
Ref117Alzheimer's Society (UK)

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