1. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.
- Author
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Archer NP, Perez-Andreu V, Stoltze U, Scheurer ME, Wilkinson AV, Lin TN, Qian M, Goodings C, Swartz MD, Ranjit N, Rabin KR, Peckham-Gregory EC, Plon SE, de Alarcon PA, Zabriskie RC, Antillon-Klussmann F, Najera CR, Yang JJ, and Lupo PJ
- Subjects
- Adolescent, Alleles, Child, Child, Preschool, Female, Genetic Association Studies, Genotype, Guatemala, Humans, Infant, Infant, Newborn, Male, Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Texas, DNA-Binding Proteins genetics, Exome, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Transcription Factors genetics
- Abstract
We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.
- Published
- 2017
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