Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
  • Berndt, Sonja I.
  • Camp, Nicola J.
  • Skibola, Christine F.
  • Vijai, Joseph
  • Wang, Zhaoming
  • ... Park, Ju-Hyun
  • 외 120명
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초록

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 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 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.

키워드

FAS GENE-MUTATIONSSUSCEPTIBILITY LOCIFOLLICULAR LYMPHOMACOMMON VARIATIONRISKVARIANTSBANK1PRIORITIZATIONCLASSIFICATIONIDENTIFICATION
제목
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
저자
Berndt, Sonja I.Camp, Nicola J.Skibola, Christine F.Vijai, JosephWang, ZhaomingGu, JianNieters, AlexandraKelly, Rachel S.Smedby, Karin E.Monnereau, AlainCozen, WendyCox, AngelaWang, Sophia S.Lan, QingTeras, Lauren R.Machado, MoaraYeager, MeredithBrooks-Wilson, Angela R.Hartge, PatriciaPurdue, Mark P.Birmann, Brenda M.Vajdic, Claire M.Cocco, PierluigiZhang, YaweiGiles, Graham G.Zeleniuch-Jacquotte, AnneLawrence, CharlesMontalvan, RebeccaBurdett, LaurieHutchinson, AmyYe, YuanqingCall, Timothy G.Shanafelt, Tait D.Novak, Anne J.Kay, Neil E.Liebow, MarkCunningham, Julie M.Allmer, CristineHjalgrim, HenrikAdami, Hans-OlovMelbye, MadsGlimelius, BengtChang, Ellen T.Glenn, MarthaCurtin, KarenCannon-Albright, Lisa A.Diver, W. RyanLink, Brian K.Weiner, George J.Conde, LuciaBracci, Paige M.Riby, JacquesArnett, Donna K.Zhi, DeguiLeach, Justin M.Holly, Elizabeth A.Jackson, Rebecca D.Tinker, Lesley F.Benavente, YolandaSala, NuriaCasabonne, DelphineBecker, NikolausBoffetta, PaoloBrennan, PaulForetova, LenkaMaynadie, MarcMcKay, JamesStaines, AnthonyChaffee, Kari G.Achenbach, Sara J.Vachon, Celine M.Goldin, Lynn R.Strom, Sara S.Leis, Jose F.Weinberg, J. BriceCaporaso, Neil E.Norman, Aaron D.De Roos, Anneclaire J.Morton, Lindsay M.Severson, Richard K.Riboli, ElioVineis, PaoloKaaks, RudolphMasala, GiovannaWeiderpass, ElisabeteChirlaque, Maria-DoloresVermeulen, Roel C. H.Travis, Ruth C.Southey, Melissa C.Milne, Roger L.Albanese, DemetriusVirtamo, JarmoWeinstein, StephanieClavel, JacquelineZheng, TongzhangHolford, Theodore R.Villano, Danylo J.Maria, AnnSpinelli, John J.Gascoyne, Randy D.Connors, Joseph M.Bertrand, Kimberly A.Giovannucci, EdwardKraft, PeterKricker, AnneTurner, JennyEnnas, Maria GraziaFerri, Giovanni M.Miligi, LuciaLiang, LimingMa, BaoshanHuang, JinyanCrouch, SimonPark, Ju-HyunChatterjee, NilanjanNorth, Kari E.Snowden, John A.Wright, JoshFraumeni, Joseph F.Offit, KennethWu, Xifengde Sanjose, SilviaCerhan, James R.Chanock, Stephen J.Rothman, NathanielSlager, Susan L.
DOI
10.1038/ncomms10933
발행일
2016-03
유형
Article
저널명
Nature Communications
7