Title | PopCluster: an algorithm to identify genetic variants with ethnicity-dependent effects. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Gurinovich, A, Bae, H, Farrell, JJ, Andersen, SL, Monti, S, Puca, A, Atzmon, G, Barzilai, N, Perls, TT, Sebastiani, P |
Journal | Bioinformatics |
Volume | 35 |
Issue | 17 |
Pagination | 3046-3054 |
Date Published | 09/2019 |
ISSN | 1367-4811 |
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 (>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. |
DOI | 10.1093/bioinformatics/btz017 |
Alternate Journal | Bioinformatics |
PubMed ID | 30624692 |
Grant List | R21 AG056630 / AG / NIA NIH HHS / United States U01 AG023755 / AG / NIA NIH HHS / United States U19 AG023122 / AG / NIA NIH HHS / United States |