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

(2015) ALZHEIMERS & DEMENTIA. 11(12). p.1452-1460
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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 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.
Keywords
GENOME-WIDE ASSOCIATION, IDENTIFIES VARIANTS, COMMON VARIANTS, DEMENTIA, APOE, CLU, CD2AP, EPHA1, LOCI, CD33, Alzheimer's disease, Genetic risk profile, Genotype-phenotype, correlation, CSFA beta(1-42), Onset age, Family history

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MLA
Sleegers, Kristel, et al. “A 22-Single Nucleotide Polymorphism Alzheimer’s Disease Risk Score Correlates with Family History, Onset Age, and Cerebrospinal Fluid Aβ42.” ALZHEIMERS & DEMENTIA, vol. 11, no. 12, 2015, pp. 1452–60, doi:10.1016/j.jalz.2015.02.013.
APA
Sleegers, K., Bettens, K., De Roeck, A., Van Cauwenberghe, C., Cuyvers, E., Verheijen, J., … Dermaut, B. (2015). A 22-single nucleotide polymorphism Alzheimer’s disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42. ALZHEIMERS & DEMENTIA, 11(12), 1452–1460. https://doi.org/10.1016/j.jalz.2015.02.013
Chicago author-date
Sleegers, Kristel, Karolien Bettens, Arne De Roeck, Caroline Van Cauwenberghe, Elise Cuyvers, Jan Verheijen, Hanne Struyfs, et al. 2015. “A 22-Single Nucleotide Polymorphism Alzheimer’s Disease Risk Score Correlates with Family History, Onset Age, and Cerebrospinal Fluid Aβ42.” ALZHEIMERS & DEMENTIA 11 (12): 1452–60. https://doi.org/10.1016/j.jalz.2015.02.013.
Chicago author-date (all authors)
Sleegers, Kristel, 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, the BELNEU consortium, Patrick Santens, Jan De Bleecker, Anne Sieben, and Bart Dermaut. 2015. “A 22-Single Nucleotide Polymorphism Alzheimer’s Disease Risk Score Correlates with Family History, Onset Age, and Cerebrospinal Fluid Aβ42.” ALZHEIMERS & DEMENTIA 11 (12): 1452–1460. doi:10.1016/j.jalz.2015.02.013.
Vancouver
1.
Sleegers K, Bettens K, De Roeck A, Van Cauwenberghe C, Cuyvers E, Verheijen J, et al. A 22-single nucleotide polymorphism Alzheimer’s disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42. ALZHEIMERS & DEMENTIA. 2015;11(12):1452–60.
IEEE
[1]
K. Sleegers et al., “A 22-single nucleotide polymorphism Alzheimer’s disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42,” ALZHEIMERS & DEMENTIA, vol. 11, no. 12, pp. 1452–1460, 2015.
@article{8547533,
  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 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.},
  author       = {Sleegers, Kristel and Bettens, Karolien and De Roeck, Arne and Van Cauwenberghe, Caroline and Cuyvers, Elise and Verheijen, Jan and Struyfs, Hanne and Van Dongen, Jasper and Vermeulen, Steven and Engelborghs, Sebastiaan and Vandenbulcke, Mathieu and Vandenberghe, Rik and De Deyn, Peter Paul and Van Broeckhoven, Christine and BELNEU consortium, the and Santens, Patrick and De Bleecker, Jan and Sieben, Anne and Dermaut, Bart},
  issn         = {1552-5260},
  journal      = {ALZHEIMERS & DEMENTIA},
  keywords     = {GENOME-WIDE ASSOCIATION,IDENTIFIES VARIANTS,COMMON VARIANTS,DEMENTIA,APOE,CLU,CD2AP,EPHA1,LOCI,CD33,Alzheimer's disease,Genetic risk profile,Genotype-phenotype,correlation,CSFA beta(1-42),Onset age,Family history},
  language     = {eng},
  number       = {12},
  pages        = {1452--1460},
  title        = {A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42},
  url          = {http://dx.doi.org/10.1016/j.jalz.2015.02.013},
  volume       = {11},
  year         = {2015},
}

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