Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease

被引：0

作者：

Ge, Yi-Jun ^{[1
,2
,3
]}

Chen, Shi-Dong ^{[1
,2
,3
]}

Wu, Bang-Sheng ^{[1
,2
,3
]}

Zhang, Ya-Ru ^{[1
,2
,3
]}

Wang, Jun ^{[4
,5
]}

He, Xiao-Yu ^{[1
,2
,3
]}

Liu, Wei-Shi ^{[1
,2
,3
]}

Chen, Yi-Lin ^{[1
,2
,3
]}

Ou, Ya-Nan ^{[6
]}

Shen, Xue-Ning ^{[1
,2
,3
]}

Huang, Yu-Yuan ^{[1
,2
,3
]}

Gan, Yi-Han ^{[1
,2
,3
]}

Yang, Liu ^{[1
,2
,3
]}

Ma, Ling-Zhi ^{[6
]}

Ma, Ya-Hui ^{[7
]}

Chen, Ke-Liang ^{[1
,2
,3
]}

Chen, Shu-Fen ^{[1
,2
,3
]}

Cui, Mei ^{[1
,2
,3
]}

Tan, Lan ^{[6
]}

Dong, Qiang ^{[1
,2
,3
]}

Zhao, Qian-Hua ^{[1
,2
,3
]}

Wang, Yan-Jiang ^{[4
,5
]}

Jia, Jian-Ping ^{[8
,9
]}

Yu, Jin-Tai ^{[1
,2
,3
]}

机构：

[1] Fudan Univ, Shanghai Med Coll, Natl Ctr Neurol Disorders, Dept Neurol, Shanghai, Peoples R China

[2] Fudan Univ, Huashan Hosp, Inst Neurol, Natl Ctr Neurol Disorders,State Key Lab Med Neurob, Shanghai, Peoples R China

[3] Fudan Univ, Shanghai Med Coll, MOE Frontiers Ctr Brain Sci, Natl Ctr Neurol Disorders, Shanghai, Peoples R China

[4] Third Mil Med Univ, Daping Hosp, Dept Neurol, 10 Changjiang Branch Rd, Chongqing 400042, Peoples R China

[5] Third Mil Med Univ, Daping Hosp, Ctr Clin Neurosci, 10 Changjiang Branch Rd, Chongqing 400042, Peoples R China

[6] Qingdao Univ, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China

[7] Qingdao Univ, Dept Neurol, Affiliated Hosp, Qingdao, Peoples R China

[8] Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Natl Clin Res Ctr Geriatr Dis, Changchun St 45, Beijing 100053, Peoples R China

[9] Capital Med Univ, Xuanwu Hosp, Natl Clin Res Ctr Geriatr Dis, Dept Neurol, Changchun St 45, Beijing 100053, Peoples R China

来源：

ALZHEIMERS & DEMENTIA | 2024年

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; ancestry; Asian; genome-wide association study; neurology; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; APOLIPOPROTEIN-E; RISK LOCI; VITAMIN-B12; RECOMMENDATIONS; POLYMORPHISM; POPULATION;

D O I：

10.1002/alz.14121

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

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