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Alzheimers Dement. 2015 Dec;11(12):1452-1460. doi: 10.1016/j.jalz.2015.02.013. Epub 2015 Jun 15.

A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42.

Author information

1
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: kristel.sleegers@molgen.vib-ua.be.
2
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
3
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
4
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Antwerp, Belgium.
5
Department of Old Age Psychiatry and Memory Clinic, University of Leuven and University Hospitals Leuven Gasthuisberg, Leuven, Belgium.
6
Laboratory for Cognitive Neurology, Department of Neurology, University of Leuven and University Hospitals Leuven Gasthuisberg, Leuven, Belgium.
7
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Antwerp, Belgium; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
8
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: christine.vanbroeckhoven@molgen.vib-ua.be.

Abstract

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.

KEYWORDS:

Alzheimer's disease; CSF Aβ(1–42); Family history; Genetic risk profile; Genotype-phenotype correlation; Onset age

PMID:
26086184
DOI:
10.1016/j.jalz.2015.02.013
[Indexed for MEDLINE]
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