The role of ECE1 variants in cognitive ability in old age and Alzheimer’s disease risk

Gillian Hamilton, Sarah E. Harris, Gail Davies, David C. Liewald, Albert Tenesa, Antony Payton, Michael A. Horan, William E R Ollier, Neil Pendleton, The Genetic and Environmental Risk for Alzheimer’s disease (GERAD1) consortium

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The β-amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. We have evaluated variants in seven Aβ-degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, and TF) for association with AD risk in the Genetic and Environmental Risk in Alzheimer's Disease Consortium 1 (GERAD1) cohort, and with three cognitive phenotypes in the Lothian Birth Cohort 1936 (LBC1936), using 128 and 121 SNPs, respectively. In GERAD1, we identified a significant association between a four-SNP intragenic ECE1 haplotype and risk of AD in individuals that carried at least one APOE ε4 allele (P=0.00035, odds ratio=1.61). In LBC1936, we identified a significant association between a different two-SNP ECE1 intragenic haplotype and non-verbal reasoning in individuals lacking the APOE ε4 allele (P=0.00036, β=-0.19). Both results showed a trend towards significance after permutation (0.05A (rs213045). We observed significantly less expression from the 338A variant in two human neuroblastoma cell lines and speculate that this promoter may be subject to tissue-specific regulation. © 2012 Wiley Periodicals, Inc.
    Original languageEnglish
    Pages (from-to)696-709
    Number of pages13
    JournalAmerican Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
    Volume159B
    Issue number6
    DOIs
    Publication statusPublished - Sept 2012

    Keywords

    • Cognition
    • Cohort study
    • Functional variant
    • Genetics
    • Tissue-specific regulation

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