Harerimana Nadia V, Goate Alison M, Bowles Kathryn R
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Aging Neurosci. 2022 Oct 20;14:1021918. doi: 10.3389/fnagi.2022.1021918. eCollection 2022.
Advances in genomic research over the last two decades have greatly enhanced our knowledge concerning the genetic landscape and pathophysiological processes involved in multiple neurodegenerative diseases. However, current insights arise almost exclusively from studies on individuals of European ancestry. Despite this, studies have revealed that genetic variation differentially impacts risk for, and clinical presentation of neurodegenerative disease in non-European populations, conveying the importance of ancestry in predicting disease risk and understanding the biological mechanisms contributing to neurodegeneration. We review the genetic influence of two important disease-associated loci, 17q21.31 (the " locus") and , to neurodegenerative disease risk in non-European populations, touching on global population differences and evolutionary genetics by ancestry that may underlie some of these differences. We conclude there is a need to increase representation of non-European ancestry individuals in genome-wide association studies (GWAS) and biomarker analyses in order to help resolve existing disparities in understanding risk for, diagnosis of, and treatment for neurodegenerative diseases in diverse populations.
在过去二十年中,基因组研究的进展极大地增进了我们对多种神经退行性疾病所涉及的遗传格局和病理生理过程的了解。然而,目前的见解几乎完全来自对欧洲血统个体的研究。尽管如此,研究表明,遗传变异对非欧洲人群神经退行性疾病的风险和临床表现有不同影响,这表明血统在预测疾病风险和理解导致神经退行性变的生物学机制方面具有重要性。我们综述了两个重要的疾病相关基因座17q21.31(“该基因座”)和 对非欧洲人群神经退行性疾病风险的遗传影响,探讨了可能是这些差异基础的全球人群差异和按血统分类的进化遗传学。我们得出结论,有必要增加非欧洲血统个体在全基因组关联研究(GWAS)和生物标志物分析中的代表性,以帮助解决目前在理解不同人群神经退行性疾病风险、诊断和治疗方面存在的差异。