Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population

• Published in: Neurobiology of aging Vol. 35; no. 4; pp. 936.e5 - 936.e12
• Main Authors: Omoumi, Ardeshir, Fok, Alice, Greenwood, Talitha, Sadovnick, A. Dessa, Feldman, Howard H., Hsiung, Ging-Yuek R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2014
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Aged; Aged, 80 and over; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoprotein E4 - genetics; BIN1; Canada - epidemiology; Canadian; Case-Control Studies; CD33; Cohort Studies; Cohorts; CR1; Female; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genotype; Humans; Internal Medicine; Male; Membrane Transport Proteins - genetics; Neurology; Nuclear Proteins - genetics; Polymorphism, Single Nucleotide; Prevalence; Receptors, Complement 3b - genetics; Risk; Sialic Acid Binding Ig-like Lectin 3 - genetics; TOMM40; Tumor Suppressor Proteins - genetics; Canada; CR1; TOMM40; BIN1; Canadian; Cohorts; Alzheimer's disease; CD33
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2013.09.025

We performed case-control studies using 2 Canadian cohorts to examine the role of 10 promising Alzheimer's disease (AD) loci identified in recent genomewide association studies. Patients age 65 years and older diagnosed with AD at baseline (prevalent cases) or who developed AD during follow-up assessments (incident cases) were compared with control subjects with no cognitive impairment. Our prevalent case study comparing prevalent AD cases (n = 428) with participants with no cognitive impairment (n = 524) revealed a significant association of rs6656401 and rs3818361 (CR1), rs2075650 (TOMM40), rs7561528 (BIN1), and rs3865444 (CD33) with late-onset AD that were robust to adjustment with age and apolipoprotein E ε4 genotype. The incident case study comparing patients who developed AD during longitudinal observation (n = 152) with participants with no cognitive impairment found that rs2075650 (TOMM40) and rs3865444 (CD33) influence the risk of developing AD in this population. In addition, pooled analysis of our AD patients confirmed that CR1, TOMM40, BIN1, and CD33 contribute to late-onset AD susceptibility, in addition to apolipoprotein E.