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阿尔茨海默病和帕金森病常见基因变异的多血统人群归因风险评估

Multi-ancestry population attributable risk assessment of common genetic variation in Alzheimer's and Parkinson's diseases.

作者信息

Jones Lietsel, Cerquera-Cleves Catalina, Schuh Artur Fs, Makarious Mary B, Iwaki Hirotaka, Nalls Mike A, Noyce Alastair J, Blauwendraat Cornelis, Singleton Andrew, Mata Ignacio, Bandres-Ciga Sara

机构信息

Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

DataTecnica LLC, Washington DC, USA.

出版信息

medRxiv. 2024 Sep 25:2024.09.23.24314240. doi: 10.1101/2024.09.23.24314240.

DOI:10.1101/2024.09.23.24314240
PMID:39371162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11451675/
Abstract

Multiple scientific studies, mostly performed within European populations, have unraveled many of the genetic factors associated with Alzheimer's disease (AD) and Parkinson's disease (PD) etiologies, improving our understanding of the molecular pathways implicated in the pathogenesis of these conditions. However, there is increasing evidence that the genetic architecture of these diseases differs across ancestral populations. This raises concerns about the efficacy of therapeutic interventions crafted around genetic targets prevalent only in European ancestry populations. Such interventions neglect potentially distinctive etiological profiles, including Latino, Black/African American, and East Asian populations. In the current study, we explore Population Attributable Risk (PAR) in AD and PD etiologies and assess the proportion of disease attributed to specific genetic factors across diverse populations. Leveraging data from genome-wide association studies across four ancestries, we explore distinct and universal therapeutic targets across diverse populations. Multi-ancestral genetics research is critical to the development of successful therapeutics and treatments for neurodegenerative diseases. By offering insights into genetic disparities, we aim to inform more inclusive and effective therapeutic strategies, advancing personalized healthcare.

摘要

多项科学研究大多在欧洲人群中开展,揭示了许多与阿尔茨海默病(AD)和帕金森病(PD)病因相关的遗传因素,增进了我们对这些疾病发病机制中所涉及分子途径的理解。然而,越来越多的证据表明,这些疾病的遗传结构在不同祖先群体中存在差异。这引发了人们对围绕仅在欧洲血统人群中普遍存在的遗传靶点制定的治疗干预措施有效性的担忧。此类干预措施忽视了潜在的独特病因特征,包括拉丁裔、黑人/非裔美国人以及东亚人群。在当前的研究中,我们探讨了AD和PD病因中的人群归因风险(PAR),并评估了不同人群中特定遗传因素所致疾病的比例。利用来自四个祖先群体的全基因组关联研究数据,我们探索了不同人群中独特且通用的治疗靶点。多祖先遗传学研究对于开发成功的神经退行性疾病治疗方法至关重要。通过提供对遗传差异的见解,我们旨在为更具包容性和有效性的治疗策略提供依据,推动个性化医疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/3e7dc96d2708/nihpp-2024.09.23.24314240v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/abc5c0d034b0/nihpp-2024.09.23.24314240v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/0801fa38f37c/nihpp-2024.09.23.24314240v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/3e7dc96d2708/nihpp-2024.09.23.24314240v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/abc5c0d034b0/nihpp-2024.09.23.24314240v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/0801fa38f37c/nihpp-2024.09.23.24314240v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/12234066/3e7dc96d2708/nihpp-2024.09.23.24314240v3-f0003.jpg

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