Methotrexate clearance and presence of non-synonymous (NS) SNPs among outliers. The average methotrexate clearance (adjusted for age, gender, race, and treatment arm) was used to divide the patients into the lowest, middle, and highest tenth percentile groups (n=70 patients per decile). The number of NS SNPs did not differ among clearance decile groups (p=0.2, data not shown), whereas (A) the number of damaging NS SNPs differed by decile group (p=2.4×10⁻⁸) as did (B) the number of rare (MAF < 1%) damaging NS SNPs p=0.049). P values generated by the exact Chi-squared test.