Bandres-Ciga Sara, Faghri Faraz, Majounie Elisa, Koretsky Mathew J, Kim Jeffrey, Levine Kristin S, Leonard Hampton, Makarious Mary B, Iwaki Hirotaka, Crea Peter Wild, Hernandez Dena G, Arepalli Sampath, Billingsley Kimberley, Lohmann Katja, Klein Christine, Lubbe Steven J, Jabbari Edwin, Saffie-Awad Paula, Narendra Derek, Reyes-Palomares Armando, Quinn John P, Schulte Claudia, Morris Huw R, Traynor Bryan J, Scholz Sonja W, Houlden Henry, Hardy John, Dumanis Sonya, Riley Ekemini, Blauwendraat Cornelis, Singleton Andrew, Nalls Mike, Jeff Janina, Vitale Dan
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.
Data Tecnica International, Washington, DC 20037, USA.
medRxiv. 2023 Nov 14:2023.11.06.23298176. doi: 10.1101/2023.11.06.23298176.
Genome-wide genotyping platforms have the capacity to capture genetic variation across different populations, but there have been disparities in the representation of population-dependent genetic diversity. The motivation for pursuing this endeavor was to create a comprehensive genome-wide array capable of encompassing a wide range of neuro-specific content for the Global Parkinson's Genetics Program (GP2) and the Center for Alzheimer's and Related Dementias (CARD). CARD aims to increase diversity in genetic studies, using this array as a tool to foster inclusivity. GP2 is the first supported resource project of the Aligning Science Across Parkinson's (ASAP) initiative that aims to support a collaborative global effort aimed at significantly accelerating the discovery of genetic factors contributing to Parkinson's disease and atypical parkinsonism by generating genome-wide data for over 200,000 individuals in a multi-ancestry context. Here, we present the Illumina NeuroBooster array (NBA), a novel, high-throughput and cost-effective custom-designed content platform to screen for genetic variation in neurological disorders across diverse populations. The NBA contains a backbone of 1,914,934 variants (Infinium Global Diversity Array) complemented with custom content of 95,273 variants implicated in over 70 neurological conditions or traits with potential neurological complications. Furthermore, the platform includes over 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease-related GWAS loci across diverse populations. The NBA can identify low frequency variants and accurately impute over 15 million common variants from the latest release of the TOPMed Imputation Server as of August 2023 (reference of over 300 million variants and 90,000 participants). We envisage this valuable tool will standardize genetic studies in neurological disorders across different ancestral groups, allowing researchers to perform genetic research inclusively and at a global scale.
全基因组基因分型平台有能力捕捉不同人群的遗传变异,但在与人群相关的遗传多样性的代表性方面存在差异。开展这项工作的动机是创建一个全面的全基因组芯片,能够涵盖全球帕金森病遗传学项目(GP2)和阿尔茨海默病及相关痴呆症中心(CARD)的广泛神经特异性内容。CARD旨在增加基因研究的多样性,将这个芯片作为促进包容性的工具。GP2是“帕金森病跨学科科学联盟”(ASAP)倡议的首个受支持资源项目,该倡议旨在支持一项全球合作努力,通过在多血统背景下为超过20万人生成全基因组数据,显著加速对导致帕金森病和非典型帕金森综合征的遗传因素的发现。在此,我们展示了Illumina神经增强芯片(NBA),这是一种新颖、高通量且经济高效的定制内容平台,用于筛查不同人群神经疾病中的遗传变异。NBA包含1,914,934个变异的主干(Infinium全球多样性芯片),并辅以95,273个变异的定制内容,这些变异与70多种神经疾病或具有潜在神经并发症的性状有关。此外,该平台包括超过10,000个标签变异,以促进不同人群中神经退行性疾病相关全基因组关联研究(GWAS)位点的推算和分析。截至2023年8月,NBA能够识别低频变异,并从TOPMed推算服务器的最新版本中准确推算出超过1500万个常见变异(参考超过3亿个变异和90,000名参与者)。我们设想这个有价值的工具将使不同祖先群体的神经疾病基因研究标准化,使研究人员能够在全球范围内进行包容性的基因研究。