Genome-Wide Association Study of Susceptibility Loci for T-Cell Acute Lymphoblastic Leukemia in Children

Qian M, Zhao X, Devidas M, Yang W, Gocho Y, Smith C, Gastier-Foster JM, Li Y, Xu H, Zhang S, Jeha S, Zhai X, Sanda T, Winter SS, Dunsmore KP, Raetz EA, Carroll WL, Winick NJ, Rabin KR, Zweidler-Mckay PA, Wood B, Pui CH, Evans WE, Hunger SP, Mullighan CG, Relling MV, Loh ML, Yang JJ. Genome-Wide Association Study of Susceptibility Loci for T-Cell Acute Lymphoblastic Leukemia in Children. J Natl Cancer Inst. 2019 Dec 1;111(12):1350-1357. doi: 10.1093/jnci/djz043. PMID: 30938820; PMCID: PMC6910193.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and can arise in B or T lymphoid lineages. Although risk loci have been identified for B-ALL, the inherited basis of T-ALL is mostly unknown, with a particular paucity of genome-wide investigation of susceptibility variants in large patient cohorts. We performed a genome-wide association study (GWAS) in 1191 children with T-ALL and 12 178 controls, with independent replication using 117 cases and 5518 controls. The associations were tested using an additive logistic regression model. Top risk variants were tested for effects on enhancer activity using luciferase assay. All statistical tests were two sided.