Open AccessFamily-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility
Author(s) -
Natalie P. Archer,
Virginia Pérez-Andreu,
Ulrik Kristoffer Stoltze,
Michael E. Scheurer,
Anna V. Wilkinson,
Ting Nien Lin,
Maoxiang Qian,
Charnise Goodings,
Michael D. Swartz,
Nalini Ranjit,
Karen R. Rabin,
Erin C. PeckhamGregory,
Sharon E. Plon,
Pedro A. de Alarcón,
Ryan C. Zabriskie,
Federico AntillónKlussmann,
Cesar Najera,
Jun J. Yang,
Philip J. Lupo
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0180488
Subject(s) - single nucleotide polymorphism , medicine , exome , population , genetic association , disease , oncology , biology , genetics , exome sequencing , gene , genotype , phenotype , environmental health
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.