Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.
Philip J LawSonja I BerndtHelen E SpeedyNicola J CampGeorgina P SavaChristine F SkibolaAmy HolroydJoseph VijaiNicola J SunterAlexandra NietersSilvia BeaAlain MonnereauDavid Martin-GarciaLynn R GoldinGuillem ClotLauren R TerasInés QuintelaBrenda M BirmannSandrine JayneWendy CozenAneela MajidKarin E SmedbyQing LanClaire DeardenAngela R Brooks-WilsonAndrew G HallMark P PurdueTryfonia Mainou-FowlerClaire M VajdicGraham H JacksonPierluigi CoccoHelen MarrYawei ZhangTongzhang ZhengGraham G GilesCharles LawrenceTimothy G CallMark LiebowMads MelbyeBengt GlimeliusLarry MansouriMartha GlennKaren CurtinW Ryan DiverBrian K LinkLucia CondePaige M BracciElizabeth A HollyRebecca D JacksonLesley F TinkerYolanda BenaventePaolo BoffettaPaul BrennanMarc MaynadieJames McKayDemetrius AlbanesStephanie WeinsteinZhaoming WangNeil E CaporasoLindsay M MortonRichard K SeversonElio RiboliPaolo VineisRoel C H VermeulenMelissa C SoutheyJonathan BeesleyJacqueline ClavelSabine TopkaJohn J SpinelliPeter KraftMaria Grazia EnnasGeoffrey SummerfieldGiovanni M FerriRobert J HarrisLucia MiligiAndrew R PettittKari E NorthDavid John AllsupJoseph F FraumeniJames R BaileyKenneth OffitGuy PrattHenrik HjalgrimChris PepperStephen J ChanockChris FeganRichard RosenquistSilvia de SanjoseAngel CarracedoMartin J S DyerDaniel CatovskyElias CampoJames R CerhanJames M AllanNathanial RothmanRichard HoulstonSusan SlagerPublished in: Nature communications (2017)
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.