GWAS of ALL susceptibility in Hispanics and functional annotation of genomic variants at the ERG locus. (A) The association between genotype and ALL was evaluated by using a logistic regression model for 572 556 SNPs in 940 Hispanic ALL cases and 681 ancestry-matched non-ALL controls. Hispanics were defined on the basis of Native American genetic ancestry. P values (−log₁₀P, y-axis), estimated from the additive logistic regression test in PLINK, were plotted against respective chromosomal position (x-axis). Gene symbols were indicated for 4 loci achieving genome-wide significance threshold (P < 5 × 10⁻⁸, dashed black horizontal line): ARID5B (10q21.2), IKZF1 (7p12.2), GATA3 (10p14), and ERG (21q22.3). The novel risk locus ERG identified in this study is underlined and highlighted in blue. (B) Functional annotation of genomic variants at the ERG locus. The default tracks including genomic positions and scale for the human genome assembly February 2009 (GRCh37/hg19) are shown on the top. The SNPs significantly associated with blood cell–related traits at this locus were marked in the GWAS catalog track. The log-transformed P values for SNPs tested for association with ALL in Hispanics are shown in the bed graph. Somatic ERG deletions in ALL (commonly involving exons 3-7 or 3-9) are indicated below the gene structure. The gene structure, Assay for Transposase-Accessible Chromatin using sequencing signals in different types of hematopoietic cells,²¹  and placental mammal basewise conservation scores by phyloP are also included. CD4_Tcell, CD4⁺ T-cell; CD8_Tcell, CD8⁺ T-cell; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; Ery, erythroid; GMP, granulocyte-macrophage progenitor; HSC, hematopoietic stem cell; LMPP, lymphoid-primed multipotent progenitor; MEP, megakaryocyte-erythroid progenitor; Mono, monocyte; MPP, multipotent progenitor; NK, natural killer cell.