ArticleGenome medicine2017
Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.
Article in Genome medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Review
- Transferability of Single- and Cross-Tissue Transcriptome Imputation Models Across Ancestry Groups.Genetic epidemiology · 2025Article
- Review
- From pharmacogenetics to pharmaco-omics: Milestones and future directions.HGG advances · 2022Review
- Article
- Gene expression imputation across multiple brain regions provides insights into schizophrenia risk.Nature genetics · 2019Article
- Integration of Machine Learning Methods to Dissect Genetically Imputed Transcriptomic Profiles in Alzheimer's Disease.Frontiers in genetics · 2019Article
- Accuracy of Gene Expression Prediction From Genotype Data With PrediXcan Varies Across and Within Continental Populations.Frontiers in genetics · 2019Article
- Genetic architecture of gene expression traits across diverse populations.PLoS genetics · 2018Article
- Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundGenome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects.
methodsPrevious work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals.
resultsWe build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations.
conclusionsOur results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.
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