Journal
JOURNAL OF NEURAL TRANSMISSION
Volume 125, Issue 1, Pages 77-87Publisher
SPRINGER WIEN
DOI: 10.1007/s00702-017-1796-6
Keywords
Alzheimer's disease; Cohort study; Genotyping microarray; Pooled DNA analysis; Candidate gene identification
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Funding
- Ludwig Boltzmann Institute of Aging Research (Vienna, Austria)
- Alzheimer Forschung Initiative e.V. (AFI) [09802]
- Interdisziplinares Zentrum fur Klinische Forschung (IZKF) Grant [Z-6]
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Alzheimer's disease (AD) is a neurodegenerative disorder that preferentially affects individuals of advanced age. Heritability estimates for AD range between 60 and 80%, but only few genetic risk factors have been identified so far. In the present explorative study, we aimed at characterizing the genetic contribution to late-onset AD in participants of the Vienna Transdanube Aging (VITA) longitudinal birth cohort study in a two-step approach. First, we performed a genome-wide screen of pooled DNA samples (n = 588) to identify allele frequency differences between AD patients and non-AD individuals using life-time diagnoses made at the age of 80 (t = 60 months). This analysis suggested a high proportion of brain-expressed genes required for cell adhesion, cell signaling and cell morphogenesis, and also scored in known AD risk genes. In a second step, we confirmed associations using individual genotypes of top-ranked markers examining AD diagnoses as well as the dimensional scores: FULD and MMSE determined up to the age of 82.5 (t = 90 months). Taken together, our study proposes genes ANKS1B, ENST00000414107, LOC100505811, SLC22A14, QRFPR, ZDHHC8P1, ADAMTS3 and PPFIA1 as possible new candidates involved in the etiology of late-onset AD, with further research being needed to clarify their exact roles.
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