Flow diagram of cohorts and statistical analysis. (A) Flow diagram of cohorts under study. The difference in the number of variants called is due to the difference in sequencing types and the region of coverage. Sample exclusion comprise those (1) with missing phenotype information, (2) with M3 sub-types: t(15;17), and (3) exclusion of pretreated patients limiting the analysis to patients receiving AML-directed induction treatment. Variant exclusion consist of those (1) that are not annotated in the dbSNP database; (2) with major allele frequency (MAF) < 1% in European population based on 1000 Genomes project (excluding rare SNPs in European population); (3) with MAF <5% in our primary cohort (excluding rare SNPs in our cohort); (4) which failed with Hardy-Weinberg equilibrium P-value threshold of 10⁻⁶; and (5) which are missing in more than 70% of samples.¹⁷ (B) Statistical analyses applied. Cox proportional hazards models were applied for detecting differences in OS and RFS, whereas logistic models were used for CR, RD, and other genetic factors. In the case of ELN2017 association with SNPs, we used the Jonckheere-Terpstra test to identify ordered differences among different groups.¹⁸ SNPs significant in the univariate analysis (unadjusted P < .01) were included in a multivariable model and stratified for age and the ELN2017 classification. We also added cohort as covariate for those SNPs that were present in both AMLCG and AMLSG data sets. For comparison, we also performed multivariable models excluding the stratification for ELN2017. The P values from the multivariable models were corrected for multiple testing using the Benjamini-Hochberg method.¹⁹ CR, complete remission; RD, refractory disease; SNV, single nucleotide variant; TGCA, The Cancer Genome Atlas.