Ethnic and trans-ethnic genome-wide association studies identify new loci influencing Japanese Alzheimer’s disease risk
Open accessAbstract
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.
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Shigemizu et al. identified rs920608 on FAM47E and SCARB2 in a replication cohort.
“They identified 134 markers located in nine genes that satisfied the significance level in the discovery cohort, and their evaluation in the replication cohort revealed the presence of rs920608 on FAM47E and SCARB2.”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [27]
The Results sections on the Japanese GWAS and replication study report 134 markers in nine genes with suggestive associations and a replication association for rs920608 at the FAM47E locus (Table 1; page not provided). The expression-QTL Results link rs920608 to SCARB2 expression, but do not place the SNP on SCARB2. The claim conflates that expression link with the SNP’s location. (LLM, conf=0.88)
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- Authors
- Shigemizu, D., Mitsumori, R., Akiyama, S., Miyashita, A., Morizono, T., Higaki, S., Asanomi, Y., Hara, N., Tamiya, G., Kinoshita, K., Ikeuchi, T., Niida, S., & Ozaki, K.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Medical Genome Center, National Center for Geriatrics and Gerontology (JP)
- Brain Research Institute, Niigata University (JP)
- Tohoku University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Corresponding author
- Shigemizu, Daichi
- Ozaki, Kouichi
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2021-03-03
- Volume
- 11
- Issue
- 1
- Pages
- 151-151
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC7925686
- OpenAlex
- W3135386161
- Cited by
- 80
- References
- 54
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 12 · 2023: 17 · 2022: 10 · 2021: 3
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Agency for Medical Research and Development (JP19dk0207045, JP20km040550, JP18kk0205009, JP18kk0205012)
- The Research Funding for Longevity Sciences from the National Center for Geriatrics and Gerontology (29-45). a grant for Research on Dementia from the Japanese Ministry of Health, Labour, and Welfare.
- Takeda Science Foundation
- The Research Funding for Longevity Sciences from the National Center for Geriatrics and Gerontology (30-29),
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, genetic susceptibility loci, Japanese population, apolipoprotein E, SORL1, non-European populations, genetic risk prediction
- MeSH terms
- Alzheimer Disease, Humans, Japan, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, LDL-Receptor Related Proteins, Membrane Transport Proteins, Genome-Wide Association Study
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