TY - JOUR
T1 - Explorative results from multistep screening for potential genetic risk loci of Alzheimer’s disease in the longitudinal VITA study cohort
AU - Scholz, Claus Jürgen
AU - Weber, Heike
AU - Jungwirth, Susanne
AU - Danielczyk, Walter
AU - Reif, Andreas
AU - Tragl, Karl Heinz
AU - Fischer, Peter
AU - Riederer, Peter
AU - Deckert, Jürgen
AU - Grünblatt, Edna
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Candidate gene identification
KW - Cohort study
KW - Genotyping microarray
KW - Pooled DNA analysis
U2 - 10.1007/s00702-017-1796-6
DO - 10.1007/s00702-017-1796-6
M3 - Journal article
C2 - 29027019
AN - SCOPUS:85031433383
SN - 0300-9564
VL - 125
SP - 77
EP - 87
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 1
ER -