A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia

Sava, Georgina P.; Sunter, Nicola J.; Smedby, Karin E.; Hall, Andrew G.; Jackson, Graham H.; Allan, James M.; Speedy, Helen E.; Di Bernardo, Maria Chiara; Sava, Georgina P; Dyer, Martin J S; Holroyd, Amy; Wang, Yufei; Sunter, Nicola J; Mansouri, Larry; Juliusson, Gunnar; Smedby, Karin E; Roos, Göran; Jayne, Sandrine; Majid, Aneela; Dearden, Claire; Hall, Andrew G; Mainou-Fowler, Tryfonia; Jackson, Graham H; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Bailey, James R.; Pratt, Guy; Pepper, Chris; Fegan, Chris; Rosenquist, Richard; Catovsky, Daniel; Allan, James M; Houlston, Richard S

Abstract

Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10-9), 4q26 (rs6858698, P = 3.07 × 10-9), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10-10) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10-8). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10-7) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10-10) and 8q22.3 (rs2511714, P = 2.90 × 10-9). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL. © 2014 Nature America, Inc.

Citation

Speedy, H. E., Di Bernardo, M. C., Sava, G. P., Dyer, M. J. S., Holroyd, A., Wang, Y., Sunter, N. J., Mansouri, L., Juliusson, G., Smedby, K. E., Roos, G., Jayne, S., Majid, A., Dearden, C., Hall, A. G., Mainou-Fowler, T., Jackson, G. H., Summerfield, G., Harris, R. J., Pettitt, A. R., …Houlston, R. S. (2014). A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nature genetics, 46(1), 56-60. https://doi.org/10.1038/ng.2843

• Journal Article Type: Article
• Acceptance Date: Aug 20, 2013
• Online Publication Date: Dec 1, 2013
• Publication Date: Jan 1, 2014
• Deposit Date: Mar 22, 2018
• Journal: Nature Genetics
• Print ISSN: 1061-4036
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 46
• Issue: 1
• Pages: 56-60
• DOI: https://doi.org/10.1038/ng.2843
• Keywords: Genetics
• Public URL: https://hull-repository.worktribe.com/output/752336
• Publisher URL: https://www.nature.com/articles/ng.2843