Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy Academic Article uri icon

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  • AIMS: We investigated associations between genetic variation in candidate genes and on a genome-wide scale with warfarin maintenance dose, time in therapeutic range (TTR), and risk of major bleeding. MATERIALS & METHODS: In total, 982 warfarin-treated patients from the RE-LY trial were studied. RESULTS: After adjusting for SNPs in VKORC1 and CYP2C9, SNPs in DDHD1 (rs17126068) and NEDD4 (rs2288344) were associated with dose. Adding these SNPs and CYP4F2 (rs2108622) to a base model increased R(2) by 2.9%. An SNP in ASPH (rs4379440) was associated with TTR (-6.8% per minor allele). VKORC1 was associated with time less than INR 2.0. VKORC1 and CYP2C9 were associated with time more than INR 3.0, but not with major bleeding. CONCLUSIONS: We identified two novel genes associated with warfarin maintenance dose and one gene associated with TTR. These genes need to be replicated in an independent cohort.


  • Eriksson, Niclas
  • Wallentin, Lars
  • Berglund, Lars
  • Axelsson, Tomas
  • Connolly, Stuart
  • Eikelboom, John
  • Ezekowitz, Michael
  • Oldgren, Jonas
  • Pare, Guillaume
  • Reilly, Paul
  • Siegbahn, Agneta
  • Syvanen, Ann-Christine
  • Wadelius, Claes
  • Yusuf, Salim
  • Wadelius, Mia

publication date

  • August 2016