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Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia

Lookup NU author(s): Professor Julie Irving, Professor James Allan

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Abstract

Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence that common genetic variation influences the risk of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), identifying risk single-nucleotide polymorphisms (SNPs) localizing to 7p12.2, 9p21.3, 10q21.2 and 14q11.2. The testing of SNPs individually for an association in GWA studies necessitates the imposition of a very stringent P-value to address the issue of multiple testing. While this reduces false positives, real associations may be missed and therefore any estimate of the total heritability will be negatively biased. Using GWAS data on 823 BCP-ALL cases by considering all typed SNPs simultaneously, we have calculated that 24% of the total variation in BCP-ALL risk is accounted for common genetic variation (95% confidence interval 6-42%). Our findings provide support for a polygenic basis for susceptibility to BCP-ALL and have wider implications for future searches for novel disease-causing risk variants. Leukemia (2012) 26, 2212-2215; doi:10.1038/leu.2012.89

Publication metadata

Author(s): Enciso-Mora V, Hosking FJ, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JAE, Tomlinson IPM, Allan JM, Taylor M, Greaves M, Houlston RS

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2012

Volume: 26

Issue: 10

Pages: 2212-2215

Print publication date: 24/04/2012

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/leu.2012.89

DOI: 10.1038/leu.2012.89

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