Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study

Figures

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  Figure 1. Histograms of them distribution of warfarin stable doses in (A) Puerto Ricans recruited from VACHS and (B) tested subcohort.

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  Figure 2. Overview of study methods and analyses. (a)See Duconge et al. PLoS ONE 2016. (b)AIMs stands for ancestral informative markers.

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  Figure 3. Single nucleotide variants (SNVs) at CYP2C9 associated with warfarin (A) sensitivity (<4 mg/day) and (B) resistance (>6 mg/day) identified with NGS. P-values correspond to case-control association test performed in Puerto Ricans of the present study but colored codes represent correlation of SNVs with rs2860905 among Hispanics from 1,000 Genomes (Puerto Ricans, Colombians, Mexican Americans and Peruvians).

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  Figure 4. Single nucleotide variants (SNVs) associated with warfarin (A) sensitivity (<4 mg/day) and (B) resistance (>6 mg/day) identified with DMET Plus array.

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  Figure 5. Representation of the most frequent haplotypes found within the region spanning CYP2C9 (chr10: 96694843 to 96750251) across Puerto Ricans in warfarin and parental populations from the 1000 Genomes Project (Caucasians, Africans and Asians). Each block represents a position within the haplotype (haplotypes 1-4, H1-4). Blue blocks indicate the presence of the variant allele for each of the positions while gray blocks indicate the presence of the wild-type allele. The green block is the presence of the variant rs2860905. Red blocks represent the variants CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). The data was obtained from the 1000 Genomes Project Phase 3 with phased genotypes.

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  Figure 6. Regression model for warfarin dose requirements among Puerto Ricans. The solid line depicts perfect prediction of the model. The stabilization dose refers to the dose given after three consecutive INRs values within the range (2–3 for most of the indications). The R2 value is adjusted. MAE and MSE stand for mean absolute error and mean standard error respectively.