6533b7d3fe1ef96bd12609ea

RESEARCH PRODUCT

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Roel VermeulenRobert J. KleinLindsay M. MortonLauren R. TerasJohn A. SnowdenAngela Brooks-wilsonAngela Brooks-wilsonSonja I. BerndtPierluigi CoccoWendy CozenRebecca D. JacksonLenka ForetovaHenrik HjalgrimBruce K. ArmstrongNeil E. CaporasoMark P. PurdueItziar SalaverriaAnne J. NovakElizabeth A. HollyAnneclaire J. De RoosKenneth OffitLiming LiangPaolo VineisStephen J. ChanockAnne KrickerSophia S. WangVicki A. MorrisonGeorge J. WeinerLesley F. TinkerNilanjan ChatterjeeHans-olov AdamiHans-olov AdamiEllen T. ChangEllen T. ChangMark LiebowMark C. LanasaLisa A. Cannon-albrightLisa A. Cannon-albrightAndrew D. ZelenetzClaire M. VajdicSara J. AchenbachJames MckayGianluca SeveriKari E. NorthEdward GiovannucciRudolf KaaksAngela CoxKarin E. SmedbySusan L. SlagerAaron D. NormanBrian K. LinkCharles E. LawrenceAmy HutchinsonJarmo VirtamoKari G. RabeTheodore R. HolfordJoshua N. SampsonLucia CondeLucia CondeTimothy G. CallAlice H. WangJulie M. CunninghamDemetrius AlbanesNikolaus BeckerElio RiboliAlain MonnereauFrancine LadenCeline M. VachonCharles C. ChungRuth C. TravisBrandt JonesBrenda M. BirmannNathaniel RothmanYolanda BenaventeKevin B. JacobsTait D. ShanafeltRachel S. KellyAnthony StainesMarc MaynadiéLucia MiligiPaul BrennanSilvia De SanjoséKaren CurtinTongzhang ZhengSílvia BeàBengt GlimeliusBengt GlimeliusElias CampoW. Ryan DiverJeffrey YuengerQing LanPeter KraftKimberly A. BertrandLaurie BurdetteMartha GlennJenny TurnerJ. Brice WeinbergJu-hyun ParkPaolo BoffettaJacqueline ClavelJoseph F. FraumeniMartyn T. SmithLogan G. SpectorLynn R. GoldinMads MelbyePaige M. BracciDavid Martín-garcíaSara S. StromChristine F. SkibolaChristine F. SkibolaVijai JosephNicola J. CampDimitrios TrichopoulosDimitrios TrichopoulosRichard K. SeversonElisabete WeiderpassJames R. CerhanMaria Grazia EnnasCarlos López-otínYawei ZhangJose F. LeisAngel CarracedoGraham G. GilesPatricia HartgeMaría Dolores ChirlaqueZhaoming WangMartha S. LinetJohn J. SpinelliAlexandra NietersAnne Zeleniuch-jacquotteGiovanni Maria FerriStephanie J. WeinsteinMeredith YeagerGiovanna MasalaNeil E. KayJacques RibySimon CrouchJosh Wright

subject

RiskLinkage disequilibriumChronic lymphocytic leukemiaSingle-nucleotide polymorphismLocus (genetics)Genome-wide association studyBiologyPolymorphism Single NucleotideLinkage DisequilibriumArticleGeneticsmedicineHumansGenetic Predisposition to DiseaseLeucèmia limfocítica crònicaGenome-wide association studies (GWAS)B-cell lymphomachronic lymphocytic leukemia or small lymphocytic lymphoma (CLL)Genetic associationRecombination GeneticGeneticsGenomicsmedicine.diseaseLeukemia Lymphocytic Chronic B-CellGenòmicaLeukemiaGenetic LociCase-Control StudiesChromosomes Human Pair 2Chronic lymphocytic leukemiaGenome-Wide Association Study

description

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 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 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. © 2013 Nature America, Inc. All rights reserved.

yearjournalcountryeditionlanguage
2013-08-01
10.1038/ng.2652http://hdl.handle.net/11585/675519