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

作者：Sleegers Kristel^*; Bettens Karolien; De Roeck Arne; Van Cauwenberghe Caroline; Cuyvers Elise; Verheijen Jan; Struyfs Hanne; Van Dongen Jasper; Vermeulen Steven; Engelborghs Sebastiaan; Vandenbulcke Mathieu; Vandenberghe Rik; De Deyn Peter Paul; Van Broeckhoven Christine

来源：Alzheimer's and Dementia, 2015, 11(12): 1452-1460.

DOI：10.1016/j.jalz.2015.02.013

• Alzheimer's disease
• Genetic risk profile
• Genotype-phenotype correlation
• CSFA beta(1-42)
• Onset age
• Family history

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.

• 出版日期2015-12