Abstract

Alzheimer’s disease (AD) has no cure, but early detection and risk prediction could allow earlier intervention. Genetic risk factors may differ between ethnic populations. To discover novel susceptibility loci of AD in the Japanese population, we conducted a genome-wide association study (GWAS) with 3962 AD cases and 4074 controls. Out of 4,852,957 genetic markers that passed stringent quality control filters, 134 in nine loci, including APOE and SORL1, were convincingly associated with AD. Lead SNPs located in seven novel loci were genotyped in an independent Japanese AD case–control cohort. The novel locus FAM47E reached genome-wide significance in a meta-analysis of association results. This is the first report associating the FAM47E locus with AD in the Japanese population. A trans-ethnic meta-analysis combining the results of the Japanese data sets with summary statistics from stage 1 data of the International Genomics of Alzheimer’s Project identified an additional novel susceptibility locus in OR2B2. Our data highlight the importance of performing GWAS in non-European populations.

Details

Title
Ethnic and trans-ethnic genome-wide association studies identify new loci influencing Japanese Alzheimer’s disease risk
Author
Shigemizu Daichi 1   VIAFID ORCID Logo  ; Mitsumori Risa 2 ; Akiyama Shintaro 2 ; Miyashita Akinori 3   VIAFID ORCID Logo  ; Morizono Takashi 2 ; Higaki Sayuri 2 ; Asanomi Yuya 2 ; Hara Norikazu 3 ; Tamiya Gen 4 ; Kinoshita Kengo 5   VIAFID ORCID Logo  ; Ikeuchi Takeshi 3   VIAFID ORCID Logo  ; Niida Shumpei 2 ; Ozaki Kouichi 6   VIAFID ORCID Logo 

1  Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan (GRID:grid.419257.c) (ISNI:0000 0004 1791 9005); Medical Research Institute, Tokyo Medical and Dental University (TMDU), Department of Medical Science Mathematics, Tokyo, Japan (GRID:grid.265073.5) (ISNI:0000 0001 1014 9130); RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (GRID:grid.265073.5) 
2  Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan (GRID:grid.419257.c) (ISNI:0000 0004 1791 9005) 
3  Brain Research Institute, Niigata University, Department of Molecular Genetics, Niigata, Japan (GRID:grid.260975.f) (ISNI:0000 0001 0671 5144) 
4  Tohoku University, Tohoku Medical Megabank Organization, Sendai, Japan (GRID:grid.69566.3a) (ISNI:0000 0001 2248 6943); Statistical Genetics Team, RIKEN Center for Advanced Intelligence Project, Tokyo, Japan (GRID:grid.7597.c) (ISNI:0000000094465255) 
5  Tohoku University, Tohoku Medical Megabank Organization, Sendai, Japan (GRID:grid.69566.3a) (ISNI:0000 0001 2248 6943); Graduate School of Information Sciences, Tohoku University, Sendai, Japan (GRID:grid.69566.3a) (ISNI:0000 0001 2248 6943) 
6  Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan (GRID:grid.419257.c) (ISNI:0000 0004 1791 9005); RIKEN Center for Integrative Medical Sciences, Yokohama, Japan (GRID:grid.419257.c) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41398-021-01272-3
ProQuest document ID
2495180773
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.