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GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21

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Listed:
  • Joseph L. Wiemels

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco
    University of Southern California)

  • Kyle M. Walsh

    (University of California San Francisco
    University of California San Francisco)

  • Adam J. Smith

    (University of California San Francisco)

  • Catherine Metayer

    (University of California Berkeley)

  • Semira Gonseth

    (University of California San Francisco
    University of Southern California)

  • Helen M. Hansen

    (University of California San Francisco)

  • Stephen S. Francis

    (University of California San Francisco
    University of Nevada Reno)

  • Juhi Ojha

    (University of California San Francisco)

  • Ivan Smirnov

    (University of California San Francisco)

  • Lisa Barcellos

    (University of California Berkeley)

  • Xiaorong Xiao

    (University of California Berkeley)

  • Libby Morimoto

    (University of California Berkeley)

  • Roberta McKean-Cowdin

    (University of Southern California)

  • Rong Wang

    (Yale University)

  • Herbert Yu

    (University of Hawaii Cancer Center)

  • Josephine Hoh

    (Yale University)

  • Andrew T. DeWan

    (Yale University)

  • Xiaomei Ma

    (Yale University)

Abstract

Childhood acute lymphoblastic leukemia (ALL) (age 0–14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children’s Oncology Group and the California Childhood Leukemia Study. Here we identify new risk loci on 17q12 near IKZF3/ZPBP2/GSDMB/ORMDL3, a locus encompassing a transcription factor important for lymphocyte development (IKZF3), and at an 8q24 region known for structural contacts with the MYC oncogene. These new risk loci may impact gene expression via local (four 17q12 genes) or long-range (8q24) interactions, affecting function of well-characterized hematopoietic and growth-regulation pathways.

Suggested Citation

  • Joseph L. Wiemels & Kyle M. Walsh & Adam J. Smith & Catherine Metayer & Semira Gonseth & Helen M. Hansen & Stephen S. Francis & Juhi Ojha & Ivan Smirnov & Lisa Barcellos & Xiaorong Xiao & Libby Morimo, 2018. "GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02596-9
    DOI: 10.1038/s41467-017-02596-9
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