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12.10.2017 | Neurology and Preclinical Neurological Studies - Original Article

Explorative results from multistep screening for potential genetic risk loci of Alzheimer’s disease in the longitudinal VITA study cohort

verfasst von: Claus-Jürgen Scholz, Heike Weber, Susanne Jungwirth, Walter Danielczyk, Andreas Reif, Karl-Heinz Tragl, Peter Fischer, Peter Riederer, Jürgen Deckert, Edna Grünblatt

Erschienen in: Journal of Neural Transmission | Ausgabe 1/2018

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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.

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Titel: Explorative results from multistep screening for potential genetic risk loci of Alzheimer’s disease in the longitudinal VITA study cohort
verfasst von: Claus-Jürgen Scholz
Heike Weber
Susanne Jungwirth
Walter Danielczyk
Andreas Reif
Karl-Heinz Tragl
Peter Fischer
Peter Riederer
Jürgen Deckert
Edna Grünblatt
Publikationsdatum: 12.10.2017
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 1/2018
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-017-1796-6

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Explorative results from multistep screening for potential genetic risk loci of Alzheimer’s disease in the longitudinal VITA study cohort

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