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Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.
Ge, Yi-Jun; Chen, Shi-Dong; Wu, Bang-Sheng; Zhang, Ya-Ru; Wang, Jun; He, Xiao-Yu; Liu, Wei-Shi; Chen, Yi-Lin; Ou, Ya-Nan; Shen, Xue-Ning; Huang, Yu-Yuan; Gan, Yi-Han; Yang, Liu; Ma, Ling-Zhi; Ma, Ya-Hui; Chen, Ke-Liang; Chen, Shu-Fen; Cui, Mei; Tan, Lan; Dong, Qiang; Zhao, Qian-Hua; Wang, Yan-Jiang; Jia, Jian-Ping; Yu, Jin-Tai.
Afiliación
  • Ge YJ; 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.
  • Chen SD; 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.
  • Wu BS; 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.
  • Zhang YR; 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.
  • Wang J; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
  • He XY; 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.
  • Liu WS; 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.
  • Chen YL; 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.
  • Ou YN; Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
  • Shen XN; 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.
  • Huang YY; 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.
  • Gan YH; 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.
  • Yang L; 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.
  • Ma LZ; Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
  • Ma YH; Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Chen KL; 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.
  • Chen SF; 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.
  • Cui M; 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.
  • Tan L; Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
  • Dong Q; 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.
  • Zhao QH; 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.
  • Wang YJ; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
  • Jia JP; Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • Yu JT; 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.
Alzheimers Dement ; 2024 Jul 18.
Article en En | MEDLINE | ID: mdl-39023044
ABSTRACT

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. HIGHLIGHTS Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
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PubMed Links
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: China