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Prediction of clinical diagnosis of Alzheimer’s disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years

Stocker, H ; Perna, L ; Weigl, K ; Möllers, T ; Schöttker, B ; Thomsen, Hauke LU orcid ; Holleczek, B ; Rujescu, D and Brenner, H (2021) In Molecular Psychiatry 26(10). p.5812-5822
Abstract
The strongest genetic risk factor for Alzheimer’s disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excluding APOE) from the most recent genome-wide association meta-analysis data was calculated and APOE status was... (More)
The strongest genetic risk factor for Alzheimer’s disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excluding APOE) from the most recent genome-wide association meta-analysis data was calculated and APOE status was determined in 5203 participants. During follow-up, 103, 111, 58, and 359 participants were diagnosed with AD, VD, MD, and all-cause dementia, respectively. Prediction ability of AD, VD, MD, and all-cause dementia by the PRS and APOE was assessed by multiple logistic regression and receiver operating characteristic curve analyses. The PRS per standard deviation increase in score and APOE4 positivity (≥1 ε4 allele) were significantly associated with greater odds of AD (OR, 95% CI: PRS: 1.70, 1.45–1.99; APOE4: 3.34, 2.24–4.99) and AD prediction accuracy was significantly improved when adding the PRS to a base model of age, sex, and education (ASE) (c-statistics: ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the ability of APOE to discern AD with stronger associations than to VD, MD, or all-cause dementia in a prospective community-based cohort (Less)
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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Psychiatry
volume
26
issue
10
pages
5812 - 5822
publisher
Nature Publishing Group
external identifiers
  • pmid:32404947
  • scopus:85084466198
  • scopus:85084466198
ISSN
1359-4184
DOI
10.1038/s41380-020-0764-y
language
English
LU publication?
no
id
94992d4f-111e-4a80-9078-0c6dabcc12c5
date added to LUP
2020-05-18 16:32:18
date last changed
2024-04-17 09:20:31
@article{94992d4f-111e-4a80-9078-0c6dabcc12c5,
  abstract     = {{The strongest genetic risk factor for Alzheimer’s disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excluding APOE) from the most recent genome-wide association meta-analysis data was calculated and APOE status was determined in 5203 participants. During follow-up, 103, 111, 58, and 359 participants were diagnosed with AD, VD, MD, and all-cause dementia, respectively. Prediction ability of AD, VD, MD, and all-cause dementia by the PRS and APOE was assessed by multiple logistic regression and receiver operating characteristic curve analyses. The PRS per standard deviation increase in score and APOE4 positivity (≥1 ε4 allele) were significantly associated with greater odds of AD (OR, 95% CI: PRS: 1.70, 1.45–1.99; APOE4: 3.34, 2.24–4.99) and AD prediction accuracy was significantly improved when adding the PRS to a base model of age, sex, and education (ASE) (c-statistics: ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the ability of APOE to discern AD with stronger associations than to VD, MD, or all-cause dementia in a prospective community-based cohort}},
  author       = {{Stocker, H and Perna, L and Weigl, K and Möllers, T and Schöttker, B and Thomsen, Hauke and Holleczek, B and Rujescu, D and Brenner, H}},
  issn         = {{1359-4184}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{5812--5822}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Molecular Psychiatry}},
  title        = {{Prediction of clinical diagnosis of Alzheimer’s disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years}},
  url          = {{http://dx.doi.org/10.1038/s41380-020-0764-y}},
  doi          = {{10.1038/s41380-020-0764-y}},
  volume       = {{26}},
  year         = {{2021}},
}