Genome-wide association study of warfarin maintenance dose in a Brazilian sample

Parra, Esteban J. and Botton, Mariana R. and Perini, Jamila A. and Krithika, S. and Bourgeois, Stephane and Johnson, Todd A. and Tsunoda, Tatsuhiko and Pirmohamed, Munir and Wadelius, Mia and Limdi, Nita A. and Cavallari, Larisa H. and Burmester, James K. and Rettie, Allan E. and Klein, Teri E. and Johnson, Julie A. and Hutz, Mara H. and Suarez-Kurtz, Guilherme (2015) Genome-wide association study of warfarin maintenance dose in a Brazilian sample. Pharmacogenomics, 16 (11). pp. 1253-1263. ISSN 1744-8042

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Official URL: https://doi.org/10.2217/pgs.15.73

Abstract

Aim: Extreme discordant phenotype and genome-wide association (GWA) approaches were combined to explore the role of genetic variants on warfarin dose requirement in Brazilians. Methods: Patients receiving low (≤20 mg/week; n = 180) or high stable warfarin doses (≥42.5 mg/week; n = 187) were genotyped with Affymetrix Axiom® Biobank arrays. Imputation was carried out using data from the combined 1000 Genomes project. Results: Genome-wide signals (p ≤ 5 × 10-8) were identified in the well-known VKORC1 (lead SNP, rs749671; OR: 20.4; p = 1.08 × 10-33) and CYP2C9 (lead SNP, rs9332238, OR: 6.8 and p = 4.4 × 10-13) regions. The rs9332238 polymorphism is in virtually perfect LD with CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). No other genome-wide significant regions were identified in the study. Conclusion: We confirmed the important role of VKORC1 and CYP2C9 polymorphisms in warfarin dose.

Item Type: Journal Article
Keywords: 1000 Genomes Project, Brazilians, CYP2C9, extreme discordant phenotypes, genome-wide association study, VKORC1, warfarin
Faculty: ARCHIVED Faculty of Science & Technology (until September 2018)
Depositing User: Lisa Blanshard
Date Deposited: 30 Jul 2020 12:53
Last Modified: 30 Jul 2020 12:53
URI: http://arro.anglia.ac.uk/id/eprint/705728

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