Dataset Information

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

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.

SUBMITTER: Bandres-Ciga S

PROVIDER: S-EPMC10659467 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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

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

medRxiv : the preprint server for health sciences 20231114

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 diversi ...[more]

PMID: 37986980

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Project description:BackgroundDental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent.MethodsThe aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification.ResultsWe identified several suggestive loci (5 × 10-8 < P < 5 × 10-6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis.ConclusionThe results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.

Project description:The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure (BP) genetics as previous candidate genes have not been among the top loci in these scans. We used Affymetrix 500K genotyping data of KORA S3 cohort (n = 1,644; Southern-Germany) to address (i) SNP coverage in 160 BP candidate genes; (ii) the evidence for associations with BP traits in genome-wide and replication data, and haplotype analysis. In total, 160 gene regions (genic region+/-10 kb) covered 2,411 SNPs across 11.4 Mb. Marker densities in genes varied from 0 (n = 11) to 0.6 SNPs/kb. On average 52.5% of the HAPMAP SNPs per gene were captured. No evidence for association with BP was obtained for 1,449 tested SNPs. Considerable associations (P<10(-3)) were detected for the genes, where >50% of HAPMAP SNPs were tagged. In general, genes with higher marker density (>0.2 SNPs/kb) revealed a better chance to reach close to significance associations. Although, none of the detected P-values remained significant after Bonferroni correction (P<0.05/2319, P<2.15 x 10(-5)), the strength of some detected associations was close to this level: rs10889553 (LEPR) and systolic BP (SBP) (P = 4.5 x 10(-5)) as well as rs10954174 (LEP) and diastolic BP (DBP) (P = 5.20 x 10(-5)). In total, 12 markers in 7 genes (ADRA2A, LEP, LEPR, PTGER3, SLC2A1, SLC4A2, SLC8A1) revealed considerable association (P<10(-3)) either with SBP, DBP, and/or hypertension (HYP). None of these were confirmed in replication samples (KORA S4, HYPEST, BRIGHT). However, supportive evidence for the association of rs10889553 (LEPR) and rs11195419 (ADRA2A) with BP was obtained in meta-analysis across samples stratified either by body mass index, smoking or alcohol consumption. Haplotype analysis highlighted LEPR and PTGER3. In conclusion, the lack of associations in BP candidate genes may be attributed to inadequate marker coverage on the genome-wide arrays, small phenotypic effects of the loci and/or complex interaction with life-style and metabolic parameters.

Dataset Information

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

Publications

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

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