NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations

Sara Bandres-Ciga; Faraz Faghri; Elisa Majounie; Mathew J Koretsky; Jeffrey Kim; Kristin S Levine; Hampton Leonard; Mary B Makarious; Hirotaka Iwaki; Peter Wild Crea; Dena G Hernandez; Sampath Arepalli; Kimberley Billingsley; Katja Lohmann; Christine Klein; Steven J Lubbe; Edwin Jabbari; Paula Saffie-Awad; Derek Narendra; Armando Reyes-Palomares; John P Quinn; Claudia Schulte; Huw R Morris; Bryan J Traynor; Sonja W Scholz; Henry Houlden; John Hardy; Sonya Dumanis; Ekemini Riley; Cornelis Blauwendraat; Andrew Singleton; Mike Nalls; Janina Jeff; Dan Vitale

doi:10.1101/2023.11.06.23298176

NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations

medRxiv [Preprint]. 2023 Nov 14:2023.11.06.23298176. doi: 10.1101/2023.11.06.23298176.

Authors

Sara Bandres-Ciga¹, Faraz Faghri^{1

2}, Elisa Majounie³, Mathew J Koretsky¹, Jeffrey Kim^{1

4}, Kristin S Levine^{1

2}, Hampton Leonard^{1

2}, Mary B Makarious^{4

5}, Hirotaka Iwaki^{1

2}, Peter Wild Crea^{1

4}, Dena G Hernandez⁴, Sampath Arepalli⁴, Kimberley Billingsley^{1

4}, Katja Lohmann⁶, Christine Klein⁶, Steven J Lubbe^{7

8}, Edwin Jabbari⁵, Paula Saffie-Awad^{9

10

11}, Derek Narendra¹², Armando Reyes-Palomares¹³, John P Quinn¹⁴, Claudia Schulte¹⁵, Huw R Morris^{5

16}, Bryan J Traynor^{17

18}, Sonja W Scholz¹⁹, Henry Houlden^{16

20}, John Hardy^{16

21}, Sonya Dumanis¹⁶, Ekemini Riley¹⁶, Cornelis Blauwendraat^{1

4}, Andrew Singleton^{1

4}, Mike Nalls^{1

2}, Janina Jeff³, Dan Vitale^{1

2}

Affiliations

¹ 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.
² Data Tecnica International, Washington, DC 20037, USA.
³ Illumina Inc, San Diego, CA 92122.
⁴ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
⁶ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
⁷ Ken and Ruth Davee Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
⁸ Simpson Querrey Center for Neurogenetics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
⁹ Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
¹⁰ Centro de Trastornos del Movimiento (CETRAM), Santiago, Chile.
¹¹ Clínica Santa María, Santiago, Chile.
¹² Inherited Movement Disorders Unit, Neurogenetics Branch, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga, Spain.
¹⁴ Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool, UK.
¹⁵ Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tuebingen and German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany.
¹⁶ Aligning Science Against Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
¹⁷ Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA.
¹⁸ Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
¹⁹ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
²⁰ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
²¹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.

Abstract

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.

Keywords: Genotyping; Global Parkinson’s Genetics Program; NeuroBooster array; diversity; genetic screening; neurological diseases.

Publication types

Preprint

Abstract

Publication types

Grants and funding