机构：[1]Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, National Center for Neurological Disorders, Fudan University, Shanghai, China[2]Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, ThirdMilitaryMedical University, Chongqing, China[3]Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China[4]Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China[5]Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China神经科系统神经内科首都医科大学宣武医院
INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology.
基金：
Science and Technology Innovation 2030 Major Projects [2022ZD0211600]; National Natural Science Foundation of China [92249305, 82071201, 82271475]; Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]; Research Start-up Fund of Huashan Hospital [2022QD002]; Excellence 2025 Talent Cultivation Program at Fudan University [3030277001]; National Postdoctoral Program for Innovative Talents [BX20230087]; ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute; State Key Laboratory of Neurobiology; Frontiers Center for Brain Science of Ministry of Education, Fudan University
第一作者机构：[1]Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, National Center for Neurological Disorders, Fudan University, Shanghai, China
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推荐引用方式(GB/T 7714)：
Yi-Jun Ge,Shi-Dong Chen,Bang-ShengWu,et al.Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease[J].ALZHEIMERS & DEMENTIA.2024,20(9):6243-6256.doi:10.1002/alz.14121.
APA：
Yi-Jun Ge,Shi-Dong Chen,Bang-ShengWu,Ya-Ru Zhang,JunWang...&Jin-Tai Yu.(2024).Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.ALZHEIMERS & DEMENTIA,20,(9)
MLA：
Yi-Jun Ge,et al."Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease".ALZHEIMERS & DEMENTIA 20..9(2024):6243-6256
医学