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• W2829189944 abstract "Abstract Motivation Over the last decade, more diverse populations have been included in genome-wide association studies. If a genetic variant has a varying effect on a phenotype in different populations, genome-wide association studies applied to a dataset as a whole may not pinpoint such differences. It is especially important to be able to identify population-specific effects of genetic variants in studies that would eventually lead to development of diagnostic tests or drug discovery. Results In this paper, we propose PopCluster: an algorithm to automatically discover subsets of individuals in which the genetic effects of a variant are statistically different. PopCluster provides a simple framework to directly analyze genotype data without prior knowledge of subjects’ ethnicities. PopCluster combines logistic regression modeling, principal component analysis, hierarchical clustering and a recursive bottom-up tree parsing procedure. The evaluation of PopCluster suggests that the algorithm has a stable low false positive rate (∼4%) and high true positive rate (&gt;80%) in simulations with large differences in allele frequencies between cases and controls. Application of PopCluster to data from genetic studies of longevity discovers ethnicity-dependent heterogeneity in the association of rs3764814 (USP42) with the phenotype. Availability and implementation PopCluster was implemented using the R programming language, PLINK and Eigensoft software, and can be found at the following GitHub repository: https://github.com/gurinovich/PopCluster with instructions on its installation and usage. Supplementary information Supplementary data are available at Bioinformatics online." @default.
• W2829189944 created "2018-07-19" @default.
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• W2829189944 date "2019-01-08" @default.
• W2829189944 modified "2023-10-10" @default.
• W2829189944 title "PopCluster: an algorithm to identify genetic variants with ethnicity-dependent effects" @default.
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• W2829189944 doi "https://doi.org/10.1093/bioinformatics/btz017" @default.
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