Genetic stratification to identify risk groups for Alzheimer's disease

Marioni, Riccardo E., Campbell, Archie, Hagenaars, Saskia P., Nagy, Reka, Amador, Carmen, Hayward, Caroline, Porteous, David J., Visscher, Peter M. and Deary, Ian J. (2017) Genetic stratification to identify risk groups for Alzheimer's disease. Journal of Alzheimer's Disease, 57 1: 275-283. doi:10.3233/JAD-161070


Author Marioni, Riccardo E.
Campbell, Archie
Hagenaars, Saskia P.
Nagy, Reka
Amador, Carmen
Hayward, Caroline
Porteous, David J.
Visscher, Peter M.
Deary, Ian J.
Title Genetic stratification to identify risk groups for Alzheimer's disease
Journal name Journal of Alzheimer's Disease   Check publisher's open access policy
ISSN 1875-8908
1387-2877
Publication date 2017-03-04
Sub-type Article (original research)
DOI 10.3233/JAD-161070
Open Access Status DOI
Volume 57
Issue 1
Start page 275
End page 283
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher IOS Press
Language eng
Abstract Stratification by genetic risk factors for Alzheimer's disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60-70 years (subset n = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus. Additive and multiplicative effects of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta -0.04, p = 0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes (p = 0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5% of the distribution) show cognitive decrements, albeit much smaller than for APOE ɛ4ɛ4 compared to ɛ3ɛ3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD.
Formatted abstract
Stratification by genetic risk factors for Alzheimer's disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60-70 years (subset n = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus. Additive and multiplicative effects of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta -0.04, p = 0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes (p = 0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5 of the distribution) show cognitive decrements, albeit much smaller than for APOE ϵ4ϵ4 compared to ϵ3ϵ3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD.
Keyword Alzheimer's disease
Apolipoprotein E
Cognitive function
Genetics
Polygenic traits
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
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