TY  - JOUR
TI  - Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis
AV  - public
Y1  - 2018/02/20/
EP  - 1706
N2  - 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.
ID  - discovery10045023
PB  - NATL ACAD SCIENCES
KW  - Alzheimer's disease
KW  -  whole-genome sequencing
KW  -  GWAS
KW  -  risk variant
KW  -  immune
KW  -  DOPA-RESPONSIVE DYSTONIA
KW  -  GENOME-WIDE ASSOCIATION
KW  -  SICKLE-CELL-ANEMIA
KW  -  PARKINSONS-DISEASE
KW  -  PERIPHERAL-BLOOD
KW  -  JAPANESE POPULATION
KW  -  SUSCEPTIBILITY GENE
KW  -  NATIONAL INSTITUTE
KW  -  SEQUENCE DATA
KW  -  AMYLOID-BETA
VL  - 115
SP  - 1697
IS  - 8
N1  - This open access article is distributed under Creative Commons Attribution-Non Commercial No Derivatives
License 4.0 (CC BY-NC-ND).
UR  - http://dx.doi.org/10.1073/pnas.1715554115
SN  - 0027-8424
JF  - Proceedings of the National Academy of Sciences of the United States of America
A1  - Zhou, X
A1  - Chen, Y
A1  - Mok, KY
A1  - Zhao, Q
A1  - Chen, K
A1  - Chen, Y
A1  - Hardy, J
A1  - Li, Y
A1  - Fu, AKY
A1  - Guo, Q
A1  - Ip, NY
ER  -