Polymorphisms within ASTN2 gene are associated with age at onset of Alzheimer’s disease
Alzheimer’s disease (AD) is a multifactorial neurological condition associated with genetic profiles that are still not completely understood. We performed a family-based low-density genome-wide association analysis of age at onset (AAO) in AD (244 patients and their relatives) using Illumina 6 K si...
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Published in | Journal of Neural Transmission Vol. 122; no. 5; pp. 701 - 708 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Vienna
Springer Vienna
01.05.2015
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Alzheimer’s disease (AD) is a multifactorial neurological condition associated with genetic profiles that are still not completely understood. We performed a family-based low-density genome-wide association analysis of age at onset (AAO) in AD (244 patients and their relatives) using Illumina 6 K single-nucleotide polymorphisms (SNPs) panel and the FBAT-logrank statistic. We observed 10 SNPs associated with AAO in AD with
p
< 2 × 10
−3
. The most significant hit within a known gene, the neuronal protein astrotactin 2 (
ASTN2)
, was SNP rs1334071 (
p
= 8.74 × 10
−4
).
ASTN2
has been implicated in several neuropsychiatric disorders, including cognitive disorders, autism and schizophrenia. We then conducted a replication study focusing on
ASTN2
gene in a Canadian sample of 791 AD patients and 782 controls using the logrank test. Five
ASTN2
SNPs (highest association is rs16933774 with
p
= 0.0053) showed associations with AAO in this Canadian sample (
p
< 0.05). Furthermore, Kaplan–Meier survival analysis of SNP rs16933774 showed that the AAO of AD in individuals heterozygous for AG genotype of rs16933774 (median of AAO = 68.5 years) was approximately 4.5 years earlier than those individuals having the AA genotype (median of AAO = 73 years). In conclusion, a significant association of
ASTN2
genetic variants with AAO of AD in two independent samples demonstrates a role for
ASTN2
in the pathogenesis of AD. Future functional studies of this gene may help to characterize the genetic architecture of the AAO of AD. Genetic factors in AAO may be a critical factor for early AD intervention and prevention efforts. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0300-9564 1435-1463 |
DOI: | 10.1007/s00702-014-1306-z |