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- Title
Explorative results from multistep screening for potential genetic risk loci of Alzheimer's disease in the longitudinal VITA study cohort.
- Authors
Scholz, Claus-Jürgen; Weber, Heike; Jungwirth, Susanne; Danielczyk, Walter; Reif, Andreas; Tragl, Karl-Heinz; Fischer, Peter; Riederer, Peter; Deckert, Jürgen; Grünblatt, Edna
- Abstract
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.
- Subjects
GENETICS of Alzheimer's disease; ALZHEIMER'S disease risk factors; ETIOLOGY of Alzheimer's disease; GENETIC testing; HERITABILITY
- Publication
Journal of Neural Transmission, 2018, Vol 125, Issue 1, p77
- ISSN
0300-9564
- Publication type
Article
- DOI
10.1007/s00702-017-1796-6