A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid A beta(42)

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, Dec-2015, In : Alzheimers & dementia. 11, 12, p. 1452-1460 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Kristel Sleegers
  • Karolien Bettens
  • Arne De Roeck
  • Caroline Van Cauwenberghe
  • Elise Cuyvers
  • Jan Verheijen
  • Hanne Struyfs
  • Jasper Van Dongen
  • Steven Vermeulen
  • Sebastiaan Engelborghs
  • Mathieu Vandenbulcke
  • Rik Vandenberghe
  • Peter Paul De Deyn
  • Christine Van Broeckhoven
  • BELNEU Consortium

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 forADin 1162 Flanders-BelgianADpatients and 1019 controls and assessed correlations with family history, onset age, and cerebrospinal fluid (CSF) biomarkers (A beta(1-42), T-Tau, P-Tau(181P)).

Results: A GRS including all single nucleotide polymorphisms (SNPs) and age-specific APOE epsilon 4 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 Ab1-42 decreased with increasing GRS (P-onset_age 5 9.0e(-11); P-A beta = 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. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license

Original languageEnglish
Pages (from-to)1452-1460
Number of pages9
JournalAlzheimers & dementia
Issue number12
Publication statusPublished - Dec-2015


  • Alzheimer's disease, Genetic risk profile, Genotype-phenotype correlation, CSFA beta(1-42), Onset age, Family history, GENOME-WIDE ASSOCIATION, IDENTIFIES VARIANTS, COMMON VARIANTS, DEMENTIA, APOE, CLU, CD2AP, EPHA1, LOCI, CD33

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