Genetic Variation in the Ontario Neurodegenerative Disease Research Initiative
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ABSTRACT:Background/Objective:Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether theAPOEE4 allele orMAPTH1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.Methods:Genotypes were defined for their respectiveAPOEallele andMAPThaplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.Results:Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, theAPOEE2 allele was associated with decreased presentation of both AD and MCI. No associations were identified betweenMAPThaplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.Conclusion:This is the first study to concurrently analyze the association ofAPOEisoforms andMAPThaplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
