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Journal article
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
Nature genetics, v 45(8), pp 868-876
01 Aug 2013
PMCID: PMC3729927
PMID: 23770605
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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- Title
- Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- Creators
- Sonja I. Berndt - National Institutes of HealthChristine F. Skibola - University of AlabamaVijai Joseph - Mécanique et Engrenage ModerneNicola J. Camp - University of UtahAlexandra Nieters - University of FreiburgZhaoming Wang - National Institutes of HealthWendy Cozen - University of Southern CaliforniaAlain Monnereau - InsermSophia S. Wang - City Of Hope National Medical CenterRachel S. Kelly - Imperial College LondonQing Lan - National Institutes of HealthLauren R. Teras - American Cancer SocietyNilanjan Chatterjee - National Institutes of HealthCharles C. Chung - NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USAMeredith Yeager - National Institutes of HealthAngela R. Brooks-Wilson - Simon Fraser UniversityPatricia Hartge - National Institutes of HealthMark P. Purdue - National Institutes of HealthBrenda M. Birmann - Harvard UniversityBruce K. Armstrong - University of SydneyPierluigi Cocco - University of CagliariYawei Zhang - Yale UniversityGianluca Severi - Cancer Council VictoriaAnne Zeleniuch-Jacquotte - New York UniversityCharles Lawrence - WestatLaurie Burdette - National Institutes of HealthJeffrey Yuenger - National Institutes of HealthAmy Hutchinson - National Institutes of HealthKevin B. Jacobs - National Institutes of HealthTimothy G. Call - Mayo ClinicTait D. Shanafelt - Mayo ClinicAnne J. Novak - Mayo ClinicNeil E. Kay - Mayo ClinicMark Liebow - Mayo ClinicAlice H. Wang - Mayo ClinicKarin E. Smedby - Karolinska InstitutetHans-Olov Adami - Karolinska InstitutetMads Melbye - Statens Serum InstitutBengt Glimelius - Karolinska InstitutetEllen T. Chang - ExponentMartha Glenn - University of UtahKaren Curtin - University of UtahLisa A. Cannon-Albright - University of UtahBrandt Jones - University of UtahW. Ryan Diver - American Cancer SocietyBrian K. Link - University of IowaGeorge J. Weiner - University of IowaLucia Conde - University of AlabamaPaige M. Bracci - University of California, San FranciscoJacques Riby - University of California, BerkeleyElizabeth A. Holly - University of California, San FranciscoMartyn T. Smith - University of California, BerkeleyRebecca D. Jackson - The Ohio State UniversityLesley F. Tinker - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaYolanda Benavente - Inst Invest Biomed Bellvitge IDIBELL, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona, SpainNikolaus Becker - German Cancer Research CenterPaolo Boffetta - Icahn School of Medicine at Mount SinaiPaul Brennan - Centre International de Recherche sur le CancerLenka Foretova - Mécanique et Engrenage ModerneMarc Maynadie - Université de BourgogneJames McKay - Centre International de Recherche sur le CancerAnthony Staines - Dublin City UniversityKari G. Rabe - Mayo ClinicSara J. Achenbach - Mayo ClinicCeline M. Vachon - Mayo ClinicLynn R. Goldin - National Institutes of HealthSara S. Strom - The University of Texas MD Anderson Cancer CenterMark C. Lanasa - Duke UniversityLogan G. Spector - University of MinnesotaJose F. Leis - Mayo ClinicJulie M. Cunningham - Mayo ClinicJ. Brice Weinberg - Duke UniversityVicki A. Morrison - Veterans Health AdministrationNeil E. Caporaso - National Institutes of HealthAaron D. Norman - Mayo ClinicMartha S. Linet - National Institutes of HealthAnneclaire J. De Roos - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaLindsay M. Morton - National Institutes of HealthRichard K. Severson - Wayne State UniversityElio Riboli - Imperial College LondonPaolo Vineis - Imperial College LondonRudolph Kaaks - German Canc Res Ctr, Div Canc Epidemiol, Baden, SwitzerlandDimitrios Trichopoulos - Harvard UniversityGiovanna Masala - FlorenceElisabete Weiderpass - Karolinska InstitutetMara-Dolores Chirlaque - CIBERESP, Barcelona, SpainRoel C. H. Vermeulen - Univ Utrecht, Inst Risk Assessment Sci, Utrecht, NetherlandsRuth C. Travis - University of OxfordGraham G. Giles - Cancer Council VictoriaDemetrius Albanes - National Institutes of HealthJarmo Virtamo - Finnish Institute for Health and WelfareStephanie Weinstein - National Institutes of HealthJacqueline Clavel - InsermTongzhang Zheng - Yale UniversityTheodore R. Holford - Yale UniversityKenneth Offit - Memorial Sloan Kettering Cancer CenterAndrew Zelenetz - Memorial Sloan Kettering Cancer CenterRobert J. Klein - Mécanique et Engrenage ModerneJohn J. Spinelli - University of British ColumbiaKimberly A. Bertrand - Harvard UniversityFrancine Laden - Harvard UniversityEdward Giovannucci - Harvard UniversityPeter Kraft - Harvard UniversityAnne Kricker - University of SydneyJenny Turner - Macquarie UniversityClaire M. Vajdic - UNSW SydneyMaria Grazia Ennas - University of CagliariGiovanni M. Ferri - University of Bari Aldo MoroLucia Miligi - FlorenceLiming Liang - Harvard UniversityJoshua Sampson - National Institutes of HealthSimon Crouch - University of YorkJu-Hyun Park - Dongguk UniversityKari E. North - University of North Carolina at Chapel HillAngela Cox - University of SheffieldJohn A. Snowden - University of SheffieldJosh Wright - Sheffield Teaching Hosp Natl Hlth Serv NHS Fdn Tr, Dept Haematol, Sheffield, S Yorkshire, EnglandAngel Carracedo - Universidade de Santiago de CompostelaCarlos Lopez-Otin - Universidad de OviedoSilvia Bea - Universitat de BarcelonaItziar Salaverria - Universitat de BarcelonaDavid Martin-Garcia - Universitat de BarcelonaElias Campo - Universitat de BarcelonaJoseph F. Fraumeni - National Institutes of HealthSilvia de Sanjose - Inst Invest Biomed Bellvitge IDIBELL, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona, SpainHenrik Hjalgrim - Statens Serum InstitutJames R. Cerhan - Mayo ClinicStephen J. Chanock - National Institutes of HealthNathaniel Rothman - National Institutes of HealthSusan L. Slager - Mayo Clinic
- Publication Details
- Nature genetics, v 45(8), pp 868-876
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- Division of Cancer Epidemiology and Genetics, NCI, US National Institutes of Health ZIACP010170 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) G0801056B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Environmental and Occupational Health
- Web of Science ID
- WOS:000322374900008
- Scopus ID
- 2-s2.0-84881023533
- Other Identifier
- 991020099318004721
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- Web of Science research areas
- Genetics & Heredity