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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) Published
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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
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-282832DOI: 10.1038/ncomms10933ISI: 000371729200001PubMedID: 26956414OAI: oai:DiVA.org:uu-282832DiVA: diva2:917548
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Swedish Cancer Society, 02 6661Stockholm County Council, 20110209
Available from: 2016-04-07 Created: 2016-04-07 Last updated: 2017-11-30Bibliographically approved

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Glimelius, Bengt

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