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[Preprint]. 2023 Nov 14:2023.11.06.23298176.

doi: 10.1101/2023.11.06.23298176.

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

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.

PMID: 37986980
PMCID: PMC10659467
DOI: 10.1101/2023.11.06.23298176

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

Sara Bandres-Ciga et al. medRxiv. 2023.

[Preprint]. 2023 Nov 14:2023.11.06.23298176.

doi: 10.1101/2023.11.06.23298176.

Authors

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.

PMID: 37986980
PMCID: PMC10659467
DOI: 10.1101/2023.11.06.23298176

Update in

NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations.
Bandres-Ciga S, Faghri F, Majounie E, Koretsky MJ, Kim J, Levine KS, Leonard H, Makarious MB, Iwaki H, Crea PW, Hernandez DG, Arepalli S, Billingsley K, Lohmann K, Klein C, Lubbe SJ, Jabbari E, Saffie-Awad P, Narendra D, Reyes-Palomares A, Quinn JP, Schulte C, Morris HR, Traynor BJ, Scholz SW, Houlden H, Hardy J, Dumanis S, Riley E, Blauwendraat C, Singleton A, Nalls M, Jeff J, Vitale D; Global Parkinson's Genetics Program (GP2) and the Center for Alzheimer's and Related Dementias (CARD). Bandres-Ciga S, et al. Mov Disord. 2024 Nov;39(11):2039-2048. doi: 10.1002/mds.29902. Epub 2024 Sep 16. Mov Disord. 2024. PMID: 39283294 Free PMC article.

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.

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Conflict of interest statement

Competing Interests: DV, FF, HLL HI, KSL, and MAN declare that they are consultants employed by Data Tecnica International, whose participation in this is part of a consulting agreement between the US National Institutes of Health and said company. MAN also an advisor to Neuron23 Inc and Character Biosciences. SWS serves on the Scientific Advisory Council of the Lewy Body Dementia Association and the Multiple System Atrophy Coalition. S.W.S. and B.J.T. receive research support from Cerevel Therapeutics. HRM is employed by UCL. In the last 12 months he reports paid consultancy from Roche, Aprinoia, AI Therapeutics and Amylyx ; lecture fees/honoraria - BMJ, Kyowa Kirin, Movement Disorders Society. Research Grants from Parkinson’s UK, Cure Parkinson’s Trust, PSP Association, Medical Research Council, Michael J Fox Foundation. Dr Morris is a co-applicant on a patent application related to C9ORF72 - Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). Dr. Christine Klein is a Medical Advisor to Centogene and Retromer Therapeutics and Speakers’ honoraria from Desitin and Bial.

Figures

**Figure 1.. Ancestry prediction clustering for samples genotyped on the NeuroBooster array**
3 dimensional principal components analysis to group individuals based on their genetic makeup. A total of 2,793 samples from the Global Parkinson’s Genetics Program were included, including 2,373 Parkinson’s disease cases and 420 Gaucher disease cases. Each point represents a sample and the colors depict the ancestral background as shown in the color legend: EUR = orange, EAS = lemon green, AMR = yellow, AJ = lapis blue, AFR = teal blue, AAC = purple, SAS = magenta, CAS = dark pink, MDE = cerulean blue. EUR (Europe), EAS(East Asian), AMR (Latino/Admixed American), AJ (Ashkenazi Jewish), AAC (African-Admixed), AFR (African), SAS (South-Asian), CAS (Central-Asian), MDE (Middle East).

**Figure 2.. Brisbane plot showing the genomic density of SNPs on GP2 raw genotyped data generated on the NeuroBooster array**

**Figure 3.. Overview of the number of Human Gene Mutation Database disease associated variants that are present on the NeuroBooster array for the most prevalent neurodegenerative diseases.**
AD = Alzheimer’s disease, ALS = amyotrophic lateral sclerosis, FTD = frontotemporal dementia, and PD = Parkinson’s disease

**Figure 4A.. Overview of NeuroBooster array content by variant category**

**Figure 4B.. Overview of NeuroBooster array content by pathogenicity predictors**

See this image and copyright information in PMC

References

1. Fatumo S, Chikowore T, Choudhury A, et al. A roadmap to increase diversity in genomic studies. Nat. Med. 2022;28(2):243–250.[cited 2023 Aug 20] - PMC - PubMed
1. Vollstedt E-J, Schaake S, Lohmann K, et al. Embracing Monogenic Parkinson’s Disease: The MJFF Global Genetic PD Cohort. Mov. Disord. 2023;38(2):286–303. - PubMed
1. Rizig M, Bandres-Ciga S, Makarious MB, et al. Identification of genetic risk loci and causal insights associated with Parkinson’s disease in African and African admixed populations: a genome-wide association study [Internet]. Lancet Neurol. 2023;Available from: 10.1016/S1474-4422(23)00283-1 - DOI - PMC - PubMed
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This is a preprint.

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

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

Authors

Affiliations

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Abstract

Conflict of interest statement

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