Manhattan plot of P values for genome-wide SNP association with asparaginase hypersensitivity. (A) The Manhattan plot shows the negative log10 of the P values for association with asparaginase hypersensitivity vs each chromosome on the x-axis. The open circles indicate SNPs genotyped using the Affymetrix 6.0 array, whereas the open squares indicate SNPs genotyped by the Illumina Exome Beadchip array. The dashed line denotes the genome-wide threshold (P = 5 × 10−8). (B) SNPs genotyped using the Affymetrix SNP 6.0 array identified the NFATC2 rs6021191 variant associated with asparaginase hypersensitivity (P = 4.1 × 10−8, OR = 3.11, CI = 2.07-4.66). AA, subjects homozygous for the reference allele (A); TT, subjects homozygous for the variant allele (T); AT, heterozygotes. (C) Illumina Exome array genotyping identified the strongest association with the HLA-DRB1 rs17885382 variant (P = 3.2 × 10−6, OR = 1.63, CI = 1.33-2.00). CC, subjects homozygous for the reference allele (C); TT, subjects homozygous for the variant allele (T); CT, heterozygotes. Associations were determined using a general linear model adjusted for treatment, ALL immunophenotype, gender, age group, and ancestry.
