Epigenome-Wide Association Study of Acute Lymphoblastic Leukemia in Children with Down Syndrome

Background: Down syndrome (DS) is associated with an up to 30-fold increased risk of B-cell acute lymphoblastic leukemia (ALL), and DS-ALL patients have worse overall survival and increased long-term treatment-related health conditions compared with non-DS ALL patients. In a recent genome-wide association study of DS-ALL, established ALL genetic risk loci were associated with DS-ALL, with several single nucleotide polymorphisms (SNPs) conferring a larger effect on ALL risk in the context of DS than in euploidy. We performed an epigenome-wide association study (EWAS) to elucidate whether epigenetic differences at birth are associated with risk of subsequent DS-ALL.