A 22‐single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42
Open accessAbstract
INTRODUCTION: The ability to identify individuals at increased genetic risk for Alzheimer's disease (AD) may streamline biomarker and drug trials and aid clinical and personal decision making. METHODS: We evaluated the discriminative ability of a genetic risk score (GRS) covering 22 published genetic risk loci for AD in 1162 Flanders-Belgian AD patients and 1019 controls and assessed correlations with family history, onset age, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42, T-Tau, P-Tau181P). RESULTS: A GRS including all single nucleotide polymorphisms (SNPs) and age-specific APOE ε4 weights reached area under the curve (AUC) 0.70, which increased to AUC 0.78 for patients with familial predisposition. Risk of AD increased with GRS (odds ratio, 2.32 (95% confidence interval 2.08-2.58 per unit; P < 1.0e(-15)). Onset age and CSF Aβ1-42 decreased with increasing GRS (Ponset_age = 9.0e(-11); PAβ = 8.9e(-7)). DISCUSSION: The discriminative ability of this 22-SNP GRS is still limited, but these data illustrate that incorporation of age-specific weights improves discriminative ability. GRS-phenotype correlations highlight the feasibility of identifying individuals at highest susceptibility.
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PRS incorporating only genome-wide significant SNPs show only a modest improvement in disease prediction over known risk factors such as APOEε4, age, and sex.
“PRS incorporating only genome-wide significant SNPs have showed only a modest improvement in disease prediction over known risk factors such as APOEε4, age, and sex [119–121].”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [119]
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References 27 · Cited by 106
- Authors
- Sleegers, K., Bettens, K., De Roeck, A., Van Cauwenberghe, C., Cuyvers, E., Verheijen, J., Struyfs, H., Van Dongen, J., Vermeulen, S., Engelborghs, S., Vandenbulcke, M., Vandenberghe, R., De Deyn, P. P., Van Broeckhoven, C., & BELNEU consortium
- Affiliations
- University of Antwerp (BE)
- Neurodegenerative Brain Diseases Group Department of Molecular Genetics VIB Antwerp Belgium
- Universitair Ziekenhuis Leuven (BE)
- Institute Born‐Bunge, University of Antwerp Antwerp Belgium
- Corresponding author
- Sleegers, Kristel
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2015-06-15
- Volume
- 11
- Issue
- 12
- Pages
- 1452-1460
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W937788945
- Cited by
- 106
- References
- 27
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 8 · 2019: 9 · 2018: 14 · 2017: 15 · 2016: 11 · 2015: 4
- FWCI
- 10.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by-nc-nd)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Alzheimer's Disease Research Foundation (SAO‐FRA S#13023)
- Departement Economie, Wetenschap en Innovatie
- Fonds Wetenschappelijk Onderzoek (FWO G026710N)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, polygenic risk score
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Belgium, Female, Genotype, Humans, Male, Middle Aged, Peptide Fragments, Phenotype, Risk Factors, Biomarkers, Amyloid beta-Peptides, tau Proteins, Age of Onset, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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