Dataset Information

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

ABSTRACT: Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.

SUBMITTER: Kim JJ

PROVIDER: S-EPMC10786718 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

Kim Jonggeol Jeffrey JJ Vitale Dan D Otani Diego Véliz DV Lian Michelle Mulan MM Heilbron Karl K Iwaki Hirotaka H Lake Julie J Solsberg Caroline Warly CW Leonard Hampton H Makarious Mary B MB Tan Eng-King EK Singleton Andrew B AB Bandres-Ciga Sara S Noyce Alastair J AJ Blauwendraat Cornelis C Nalls Mike A MA Foo Jia Nee JN Mata Ignacio I

Nature genetics 20231228 1

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci ...[more]

PMID: 38155330

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Project description:BackgroundAsthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression.MethodsA meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10-5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico.ResultsOne hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele ) = 0.82, p = 9.05 × 10-6 and replication: ORT allele = 0.89, p = 5.35 × 10-3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele = 0.85, p = 3.10 × 10-5 and replication: ORC allele = 0.89, p = 1.30 × 10-2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood.ConclusionsThis multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Dataset Information

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

Publications

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

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