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Cohort-specific imp...
Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans
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- Gottlieb, Assaf (författare)
- University of Texas
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- Daneshjou, Roxana (författare)
- Stanford University
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- DeGorter, Marianne (författare)
- Stanford University
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- Bourgeois, Stephane (författare)
- Queen Mary University,Stanford University
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- Svensson, Peter J. (författare)
- Lund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups
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- Wadelius, Mia (författare)
- Uppsala universitet,Uppsala University,Science for Life Laboratory, SciLifeLab,Klinisk farmakogenomik och osteoporos
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- Deloukas, Panos (författare)
- Queen Mary University,King Abdulaziz University
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- Montgomery, Stephen B. (författare)
- Stanford University
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- Altman, Russ B. (författare)
- Stanford University
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(creator_code:org_t)
- 2017-11-24
- 2017
- Engelska.
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 9:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://genomemedici...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Background: Genome-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. Methods: Previous 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. Results: We 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. Conclusions: Our 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Odontologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dentistry (hsv//eng)
Nyckelord
- African Americans
- International Warfarin Pharmacogenetics Consortium
- Pharmacogenomics
- Warfarin dose
- African Americans
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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