eprintid: 10045023
rev_number: 24
eprint_status: archive
userid: 608
dir: disk0/10/04/50/23
datestamp: 2018-03-12 10:48:00
lastmod: 2021-09-19 22:21:48
status_changed: 2018-03-12 10:48:00
type: article
metadata_visibility: show
creators_name: Zhou, X
creators_name: Chen, Y
creators_name: Mok, KY
creators_name: Zhao, Q
creators_name: Chen, K
creators_name: Chen, Y
creators_name: Hardy, J
creators_name: Li, Y
creators_name: Fu, AKY
creators_name: Guo, Q
creators_name: Ip, NY
title: Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Alzheimer's disease, whole-genome sequencing, GWAS, risk variant, immune, DOPA-RESPONSIVE DYSTONIA, GENOME-WIDE ASSOCIATION, SICKLE-CELL-ANEMIA, PARKINSONS-DISEASE, PERIPHERAL-BLOOD, JAPANESE POPULATION, SUSCEPTIBILITY GENE, NATIONAL INSTITUTE, SEQUENCE DATA, AMYLOID-BETA
note: This open access article is distributed under Creative Commons Attribution-Non Commercial No Derivatives
License 4.0 (CC BY-NC-ND).
abstract: Alzheimer’s disease (AD) is a leading cause of mortality among the
elderly. We performed a whole-genome sequencing study of AD in
the Chinese population. In addition to the variants identified in or
around the APOE locus (sentinel variant rs73052335, P = 1.44 ×
10−14), two common variants, GCH1 (rs72713460, P = 4.36 × 10−5
)
and KCNJ15 (rs928771, P = 3.60 × 10−6
), were identified and further
verified for their possible risk effects for AD in three small non-Asian
AD cohorts. Genotype–phenotype analysis showed that KCNJ15 variant
rs928771 affects the onset age of AD, with earlier disease onset
in minor allele carriers. In addition, altered expression level of the
KCNJ15 transcript can be observed in the blood of AD subjects.
Moreover, the risk variants of GCH1 and KCNJ15 are associated with
changes in their transcript levels in specific tissues, as well as
changes of plasma biomarkers levels in AD subjects. Importantly,
network analysis of hippocampus and blood transcriptome datasets
suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci
might exert their functions through their regulatory effects on
immune-related pathways. Taking these data together, we identified
common variants of GCH1 and KCNJ15 in the Chinese population
that contribute to AD risk. These variants may exert their
functional effects through the immune system.
date: 2018-02-20
date_type: published
publisher: NATL ACAD SCIENCES
official_url: http://dx.doi.org/10.1073/pnas.1715554115
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1535178
doi: 10.1073/pnas.1715554115
lyricists_name: Hardy, John
lyricists_name: Mok, Kin Ying
lyricists_name: Smalley, June
lyricists_id: JHARD28
lyricists_id: BKMOK09
lyricists_id: JASMA87
actors_name: Bracey, Alan
actors_id: ABBRA90
actors_role: owner
full_text_status: public
publication: Proceedings of the National Academy of Sciences of the United States of America
volume: 115
number: 8
pagerange: 1697-1706
pages: 10
issn: 0027-8424
citation:        Zhou, X;    Chen, Y;    Mok, KY;    Zhao, Q;    Chen, K;    Chen, Y;    Hardy, J;                 ... Ip, NY; + view all <#>        Zhou, X;  Chen, Y;  Mok, KY;  Zhao, Q;  Chen, K;  Chen, Y;  Hardy, J;  Li, Y;  Fu, AKY;  Guo, Q;  Ip, NY;   - view fewer <#>    (2018)    Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis.                   Proceedings of the National Academy of Sciences of the United States of America , 115  (8)   pp. 1697-1706.    10.1073/pnas.1715554115 <https://doi.org/10.1073/pnas.1715554115>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10045023/1/1697.full.pdf