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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
Huntsman Canc Inst, Dept Internal Med, Div Hematol & Hematol Malignancies, Salt Lake City, UT 84112 USA.;Univ Utah, Sch Med, Salt Lake City, UT 84112 USA..
Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.;Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA.;Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA..
Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA..
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2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, 10933Article in journal (Refereed) PublishedText
Abstract [en]

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

Place, publisher, year, edition, pages
2016. Vol. 7, 10933
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-282832DOI: 10.1038/ncomms10933ISI: 000371729200001PubMedID: 26956414OAI: oai:DiVA.org:uu-282832DiVA: diva2:917548
Swedish Cancer Society, 02 6661Stockholm County Council, 20110209
Available from: 2016-04-07 Created: 2016-04-07 Last updated: 2016-04-07Bibliographically approved

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