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, John M Starr, David Porteous, Ian J Deary

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 (0.05 A (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
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume159B
Issue number6
Early online date14 Jun 2012
DOIs
Publication statusPublished - 2012

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