ArticlePloS one2024
Identifying key genes in COPD risk via multiple population data integration and gene prioritization.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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3 authors.
Funding
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Abstract
Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, making it a leading cause of death worldwide. Several genome-wide association studies (GWAS) have been conducted to identify loci associated with COPD. However, different ancestral genetic compositions for the same disease across various populations present challenges in studies involving multi-population data. In this study, we aimed to identify protein-coding genes associated with COPD by prioritizing genes for each population's GWAS data, and then combining these results instead of performing a common meta-GWAS due to significant sample differences in different population cohorts. Lung function measurements are often used as indicators for COPD risk prediction; therefore, we used lung function GWAS data from two populations, Japanese and European, and re-evaluated them using a multi-population gene prioritization approach. This study identified significant single nucleotide variants (SNPs) in both Japanese and European populations. The Japanese GWAS revealed nine significant SNPs and four lead SNPs in three genomic risk loci. In comparison, the European population showed five lead SNPs and 17 independent significant SNPs in 21 genomic risk loci. A comparative analysis of the results found 28 similar genes in the prioritized gene lists of both populations. We also performed a standard meta-analysis for comparison and identified 18 common genes in both populations. Our approach demonstrated that trans-ethnic linkage disequilibrium (LD) could detect some significant novel associations and genes that have yet to be reported or were missed in previous analyses. The study suggests that a gene prioritization approach for multi-population analysis using GWAS data may be a feasible method to identify new associations in data with genetic diversity across different populations. It also highlights the possibility of identifying generalized and population-specific treatment and diagnostic options.
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