PLoS ONE (Jan 2017)

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

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

DOI
https://doi.org/10.1371/journal.pone.0180488
Journal volume & issue
Vol. 12, no. 8
p. e0180488

Abstract

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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.