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

Lookup NU author(s): Dr Nicola Sunter, Dr Andrew Hall, Dr Tryfonia Mainou-Fowler, Professor Graham Jackson, Professor James Allan

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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 x 10(-9)), 4q26 (rs6858698, P = 3.07 x 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 x 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 x 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 x 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 x 10(-10)) and 8q22.3 (rs2511714, P = 2.90 x 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.


Publication metadata

Author(s): Speedy HE, Di Bernardo MC, Sava GP, Dyer MJS, Holroyd A, Wang YF, Sunter NJ, Mansouri L, Juliusson G, Smedby KE, Roos G, Jayne S, Majid A, Dearden C, Hall AG, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Rosenquist R, Catovsky D, Allan JM, Houlston RS

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2014

Volume: 46

Issue: 1

Pages: 56-60

Print publication date: 01/01/2014

Online publication date: 01/01/2014

Acceptance date: 06/11/2013

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.2843

DOI: 10.1038/ng.2843

Notes: epub:01/12/2013


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Funding

Funder referenceFunder name
National Health Service
Arbib Fund
C1298/A8362Cancer Research UK
LRF06002Leukaemia and Lymphoma Research
LRF05001Leukaemia and Lymphoma Research

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