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

Joseph L Wiemels; Kyle M Walsh; Adam J de Smith; Catherine Metayer; Semira Gonseth; Helen M Hansen; Stephen S Francis; Juhi Ojha; Ivan Smirnov; Lisa Barcellos; Xiaorong Xiao; Libby Morimoto; Roberta McKean-Cowdin; Rong Wang; Herbert Yu; Josephine Hoh; Andrew T DeWan; Xiaomei Ma

doi:10.1038/s41467-017-02596-9

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

Nat Commun. 2018 Jan 18;9(1):286. doi: 10.1038/s41467-017-02596-9.

Authors

Joseph L Wiemels^{1

2

3

4}, Kyle M Walsh^{5

6}, Adam J de Smith⁵, Catherine Metayer⁷, Semira Gonseth^{5

8}, Helen M Hansen⁶, Stephen S Francis^{5

9}, Juhi Ojha⁵, Ivan Smirnov⁶, Lisa Barcellos⁷, Xiaorong Xiao⁷, Libby Morimoto⁷, Roberta McKean-Cowdin⁸, Rong Wang¹⁰, Herbert Yu¹¹, Josephine Hoh¹⁰, Andrew T DeWan¹⁰, Xiaomei Ma¹²

Affiliations

¹ Department of Epidemiology and Biostatistics, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA. joe.wiemels@ucsf.edu.
² Department of Neurological Surgery, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA. joe.wiemels@ucsf.edu.
³ Institute for Human Genetics, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA. joe.wiemels@ucsf.edu.
⁴ Department of Preventative Medicine, University of Southern California, SSB 318D 2001 N. Soto Street, Los Angeles, CA, 90033, USA. joe.wiemels@ucsf.edu.
⁵ Department of Epidemiology and Biostatistics, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA.
⁶ Department of Neurological Surgery, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA.
⁷ School of Public Health, University of California Berkeley, 1950 University Avenue, Suite 460, Berkeley, CA, 94720, USA.
⁸ Department of Preventative Medicine, University of Southern California, SSB 318D 2001 N. Soto Street, Los Angeles, CA, 90033, USA.
⁹ Department of Epidemiology, School of Community Health Sciences, University of Nevada Reno, 1664 N. Virginia Street, Reno, NV, 89557, USA.
¹⁰ Department of Chronic Diseases Epidemiology, School of Public Health, Yale University, 60 College Street, New Haven, CT, 06520, USA.
¹¹ University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
¹² Department of Chronic Diseases Epidemiology, School of Public Health, Yale University, 60 College Street, New Haven, CT, 06520, USA. xiaomei.ma@yale.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
California
Child, Preschool
Chromosomes, Human, Pair 17 / genetics*
Chromosomes, Human, Pair 8 / genetics*
Female
Gene Frequency
Genetic Predisposition to Disease / ethnology
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study*
Hispanic or Latino / genetics
Humans
Infant
Infant, Newborn
Male
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma / ethnology
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding