A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort.
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 (ɛ4, ɛ2) 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 (nmax = 549) and elderly non-demented samples (nmax = 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; ɛ4 (OR = 1.85, 95% CI 1.35-2.52, p = <0.0001) and ɛ2 (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 ɛ4 allele.
Dementia Research Group, University of Bristol, Level 1, Learning & Research, Southmead Hospital, Bristol, UK.
Olivia Anna
OA
Skrobot
Centre for Public Health, Queen's University of Belfast, c/o Regional Genetics Centre, Level A, Tower Block, Belfast City Hospital, Belfast, UK.
Amy Jayne
AJ
McKnight
Institute of Clinical Sciences, Block B, Queens University Belfast, Royal Victoria Hospital, Belfast, UK.
Peter Anthony
PA
Passmore
Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, I.R.C.C.S. "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
Davide
D
Seripa
Institute of Gerontology and Geriatrics, University of Perugia, Ospedale S.M. della Misericordia, Perugia, Italy.
Patrizia
P
Mecocci
Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, I.R.C.C.S. "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.|Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Policlinico, Bari, Italy.
Francesco
F
Panza
Institute of Neuroscience, NIHR Biomedical Research Building, Campus for Ageing & Vitality Newcastle upon Tyne, UK.
Rajesh
R
Kalaria
Nuffield Department of Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Headington, Oxford, UK.
Gordon
G
Wilcock
MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.
Marcus
M
Munafò
Department of Neurology and Memory Research Unit, Helsinki University Central Hospital, HUS, Finland.
Timo
T
Erkinjuntti
School of Medicine, University of Tampere, Finland.|Fimlab Laboratories Ltd, Tampere University Hospital region, Finland.
Pekka
P
Karhunen
School of Medicine, University of Tampere, Finland.|Fimlab Laboratories Ltd, Tampere University Hospital region, Finland.
Tanja
T
Pessi
School of Medicine, University of Tampere, Finland.|Fimlab Laboratories Ltd, Tampere University Hospital region, Finland.
Mika
M
Martiskainen
Dementia Research Group, University of Bristol, Level 1, Learning & Research, Southmead Hospital, Bristol, UK.
Seth
S
Love
Dementia Research Group, University of Bristol, Level 1, Learning & Research, Southmead Hospital, Bristol, UK.
Patrick Gavin
PG
Kehoe
D001057:Apolipoproteins E / Q000235:genetics; D015331:Cohort Studies; D030541:Databases, Genetic; D015140:Dementia, Vascular / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics
D001057:Apolipoproteins E; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
Association; cognitive impairment; dementia; gene; meta-analysis; vascular