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种族和跨种族全基因组关联研究确定了影响日本阿尔茨海默病风险的新位点。

Ethnic and trans-ethnic genome-wide association studies identify new loci influencing Japanese Alzheimer's disease risk.

机构信息

Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.

Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan.

出版信息

Transl Psychiatry. 2021 Mar 3;11(1):151. doi: 10.1038/s41398-021-01272-3.

DOI:10.1038/s41398-021-01272-3
PMID:33654092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7925686/
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.

摘要

阿尔茨海默病（AD）目前无法治愈，但早期发现和风险预测可以实现早期干预。遗传风险因素在不同种族群体中可能存在差异。为了在日本人群中发现 AD 的新的易感基因座，我们进行了一项全基因组关联研究（GWAS），共纳入 3962 例 AD 病例和 4074 例对照。在通过严格质量控制过滤的 4852957 个遗传标记中，有 134 个位于包括 APOE 和 SORL1 在内的 9 个基因座，与 AD 有明显的关联。在一个独立的日本 AD 病例对照队列中对位于七个新基因座的先导 SNP 进行了基因分型。在对关联结果进行的荟萃分析中，新型基因座 FAM47E 达到了全基因组显著水平。这是第一个在日本人群中与 FAM47E 基因座相关的 AD 报告。一项结合了日本数据集中的结果和国际阿尔茨海默病基因组学项目第一阶段汇总统计数据的跨种族荟萃分析，确定了 OR2B2 中存在另一个新的易感基因座。我们的数据强调了在非欧洲人群中进行 GWAS 的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/7c8d3f153cdc/41398_2021_1272_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/1a1a52eac5e6/41398_2021_1272_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/a7eef8a36586/41398_2021_1272_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/b10e5b6f45ad/41398_2021_1272_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/7c8d3f153cdc/41398_2021_1272_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/1a1a52eac5e6/41398_2021_1272_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/a7eef8a36586/41398_2021_1272_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/b10e5b6f45ad/41398_2021_1272_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd3b/7925686/7c8d3f153cdc/41398_2021_1272_Fig4_HTML.jpg

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