Journal Article

Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility

Perez-Andreu, Virginia, Ranjit, Nalini, Rabin, Karen R., Zabriskie, Ryan C., Archer, Natalie P., Scheurer, Michael E., de Alarcon, Pedro A., Swartz, Michael D., Lupo, Philip J., Yang, Jun J., Najera, Cesar R., Plon, Sharon E., Goodings, Charnise, Lin, Ting-Nien, Peckham-Gregory, Erin C., Antillon-Klussmann, Federico, Stoltze, Ulrik, Wilkinson, Anna V., Qian, Maoxiang

2017

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute lymphoblastic leukemia / Acute lymphocytic leukemia / Adolescent / Alleles / Analysis / Bias / Bioinformatics / Biology and Life Sciences / Cancer / Care and treatment / Child / Child, Preschool / Childhood / Children / Children & youth / College campuses / DNA-Binding Proteins - genetics / Ethnicity / Exome / Families & family life / Female / Genetic Association Studies / Genetic Predisposition to Disease / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genotype / Guatemala / Health aspects / Health care / Health risks / Hematology / Hispanic Americans / Hispanic Americans - genetics / Hospitals / Humans / Infant / Infant, Newborn / Leukemia / Lymphatic leukemia / Male / Medicine / Medicine and Health Sciences / Minority & ethnic groups / Oncology / Pediatrics / People and Places / Pharmaceutical sciences / Polymorphism, Single Nucleotide / Population / Population genetics / Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis / Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics / Public health / Single-nucleotide polymorphism / Texas / Transcription Factors - genetics