%0 Journal Article
%@ 0027-8424
%A Zhou, X
%A Chen, Y
%A Mok, KY
%A Zhao, Q
%A Chen, K
%A Chen, Y
%A Hardy, J
%A Li, Y
%A Fu, AKY
%A Guo, Q
%A Ip, NY
%D 2018
%F discovery:10045023
%I NATL ACAD SCIENCES
%J Proceedings of the National Academy of Sciences of the United States of America
%K 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
%N 8
%P 1697-1706
%T Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis
%U https://discovery.ucl.ac.uk/id/eprint/10045023/
%V 115
%X 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.
%Z This open access article is distributed under Creative Commons Attribution-Non Commercial No Derivatives  License 4.0 (CC BY-NC-ND).