6533b871fe1ef96bd12d0f1e
RESEARCH PRODUCT
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Nathaniel RothmanYolanda BenaventePaul BrennanQing LanPierluigi CoccoSimon CrouchAnneclaire J. De RoosAnneclaire J. De RoosJosh WrightChristine F. SkibolaChristine F. SkibolaMark P. PurdueElisabete WeiderpassJames R. CerhanRandy D. GascoyneMaria Grazia EnnasKari E. NorthZhaoming WangJinyan HuangJulie M. CunninghamAlain MonnereauAlain MonnereauPeter KraftPatricia HartgeEdward GiovannucciKaren CurtinGiovanna MasalaJacqueline ClavelJacqueline ClavelNeil E. KayJacques RibyJacques RibyMaría Dolores ChirlaqueJohn J. SpinelliDelphine CasabonneJenny TurnerLucia CondeLucia CondeLesley F. TinkerMartha GlennSara S. StromDonna K. ArnettRebecca MontalvanJu-hyun ParkMelissa C. SoutheyAnn MariaKarin E. SmedbyLindsay M. MortonMarc MaynadiéLaurie BurdettAmy HutchinsonBengt GlimeliusW. Ryan DiverElio RiboliSonja I. BerndtLisa A. Cannon-albrightLisa A. Cannon-albrightKimberly A. BertrandAaron D. NormanSara J. AchenbachCeline M. VachonAngela CoxXifeng WuTheodore R. HolfordNeil E. CaporasoJoseph F. FraumeniRoel VermeulenRudolph KaaksMads MelbyeMads MelbyeJoseph VijaiKari G. ChaffeeLauren R. TerasRebecca D. JacksonLenka ForetovaJ. Brice WeinbergPaige M. BracciSophia S. WangDemetrius AlbanesStephen J. ChanockWendy CozenMark LiebowAnne J. NovakHans-olov AdamiHans-olov AdamiGeorge J. WeinerAngela Brooks-wilsonAngela Brooks-wilsonKenneth OffitAnne KrickerClaire M. VajdicJames MckayEllen T. ChangEllen T. ChangBaoshan MaBaoshan MaCristine AllmerSusan L. SlagerBrian K. LinkElizabeth A. HollyAnthony StainesLiming LiangJarmo VirtamoTimothy G. CallNicola J. CampRuth C. TravisAlexandra NietersDegui ZhiBrenda M. BirmannTait D. ShanafeltRachel S. KellyRachel S. KellyGraham G. GilesGraham G. GilesNilanjan ChatterjeeJohn A. SnowdenYuanqing YeNúria SalaTongzhang ZhengPaolo BoffettaLynn R. GoldinDanylo J. VillanoJose F. LeisPaolo VineisLucia MiligiJian GuJustin M. LeachSilvia De SanjoséRichard K. SeversonYawei ZhangHenrik HjalgrimRoger L. MilneRoger L. MilneCharles E. LawrenceMeredith YeagerMoara MachadoMoara MachadoNikolaus BeckerJoseph M. ConnorsAnne Zeleniuch-jacquotteGiovanni Maria FerriStephanie J. Weinsteinsubject
0301 basic medicineMedicin och hälsovetenskapChronic lymphocytic leukemiaGeneral Physics and AstronomyGenome-wide association studyVARIANTSMedical and Health SciencesMalalties hereditàries[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/HematologyChronicGeneticsRISKLeukemiaMultidisciplinaryBANK1VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin sosialmedisin: 801Bcl-2-Like Protein 11QAdaptor Proteins[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/HematologySingle NucleotideLymphocytic3. Good healthPRIORITIZATIONMultidisciplinary SciencesLeukemiamedicine.anatomical_structureScience & Technology - Other TopicsTRANSCRIPTION FACTOR EOMESODERMINGenetic disordersEXPRESSIONSUSCEPTIBILITY LOCIScienceEuropean Continental Ancestry GroupFAS GENE-MUTATIONSLocus (genetics)BiologyPolymorphism Single NucleotideGeneral Biochemistry Genetics and Molecular BiologyCLASSIFICATIONWhite PeopleArticle03 medical and health sciencesProto-Oncogene ProteinsMD MultidisciplinarymedicineGenetic predispositionSNPHumansLeucèmia limfocítica crònicaGenetic Predisposition to DiseasePolymorphismB cellSerpinsGenetic associationAdaptor Proteins Signal TransducingScience & TechnologySignal TransducingB-CellMembrane ProteinsGeneral Chemistrymedicine.diseaseLeukemia Lymphocytic Chronic B-Cell030104 developmental biologyChronic lymphocytic leukemiaVDP::Medical disciplines: 700::Health sciences: 800::Community medicine Social medicine: 801Apoptosis Regulatory ProteinsT-Box Domain ProteinsFOLLICULAR LYMPHOMAGenome-Wide Association Studydescription
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 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-03-01 |