Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.
Sonja I BerndtNicola J CampChristine F SkibolaJoseph VijaiZhaoming WangJian GuAlexandra NietersRachel S KellyKarin E SmedbyAlain MonnereauWendy CozenAngela CoxSophia S WangQing LanLauren R TerasMoara MachadoMeredith YeagerAngela R Brooks-WilsonPatricia HartgeMark P PurdueBrenda M BirmannClaire M VajdicPierluigi CoccoYawei ZhangGraham G GilesAnne Zeleniuch-JacquotteCharles LawrenceRebecca MontalvanLaurie BurdettAmy HutchinsonYuanqing YeTimothy G CallTait D ShanafeltAnne J NovakNeil E KayMark LiebowJulie M CunninghamCristine AllmerHenrik HjalgrimHans-Olov AdamiMads MelbyeBengt GlimeliusEllen T ChangMartha GlennKaren CurtinLisa A Cannon-AlbrightW Ryan DiverBrian K LinkGeorge J WeinerLucia CondePaige M BracciJacques RibyDonna K ArnettDegui ZhiJustin M LeachElizabeth A HollyRebecca D JacksonLesley F TinkerYolanda BenaventeNúria SalaDelphine CasabonneNikolaus BeckerPaolo BoffettaPaul BrennanLenka ForetovaMarc MaynadieJames McKayAnthony StainesKari G RabeSara J AchenbachCeline M VachonLynn R GoldinSara S StromJose F LeisJ Brice WeinbergNeil E CaporasoAaron D NormanAnneclaire J De RoosLindsay M MortonRichard K SeversonElio RiboliPaolo VineisRudolph KaaksGiovanna MasalaElisabete WeiderpassMaría-Dolores ChirlaqueRoel C H VermeulenRuth C TravisMelissa C SoutheyRoger L MilneDemetrius AlbanesJarmo VirtamoStephanie WeinsteinJacqueline ClavelTongzhang ZhengTheodore R HolfordDanylo J VillanoAnn MariaJohn J SpinelliRandy D GascoyneJoseph M ConnorsKimberly A BertrandEdward GiovannucciPeter KraftAnne KrickerJenny TurnerMaria Grazia EnnasGiovanni M FerriLucia MiligiLiming LiangBaoshan MaJinyan HuangSimon CrouchJu-Hyun ParkNilanjan ChatterjeeKari E NorthJohn A SnowdenJosh WrightJoseph F FraumeniKenneth OffitXifeng WuSilvia de SanjoseJames R CerhanStephen J ChanockNathaniel RothmanSusan L SlagerPublished in: Nature communications (2016)
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.