Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Sonja I. Berndt (1) , Nicola J. Camp , Christine F. Skibola , Joseph Vijai , Zhaoming Wang , Jian Gu , Alexandra Nieters , Rachel S. Kelly , Karin E. Smedby , Alain Monnereau , Wendy Cozen , Angela Cox , Sophia S. Wang , Qing Lan , Lauren R. Teras , Moara Ma , Meredith Ye , Angela R. Brooks-Wilson , Patricia Hartge , Mark Ma , Brenda M. Birmann , Claire M. Vajdic , Pierluigi Cocco , Yawei Zhang , Graham G. Giles , Anne Zeleniuch-Jacquotte , Charles Lawrence , Rebecca Montalvan , Laurie Burdett , Amy Hutchinson , Yuanqing Ye , Timothy G. Call , Tait D. Shanafelt , Anne Novak , Neil E. Kay , Julie M. Cunningham , Cristine Allmer , Henrik Hjalgrim , Hans-Olov Adami , Mads Ma , Bengt Glimelius , Ellen T. Chang , Martha Ma , Karen Curtin , Lisa A. Cannon-Albright , W Ryan Diver , Brian K. Link , George J. Weiner , Lucia Conde , Paige M. Bracci , Jacques Riby , Donna K. Arnett , Degui Zhi , Justin M. Leach , Elizabeth A. Holly , Rebecca D. Jackson , Lesley F. Tinker , Yolanda Benavente , Núria Sala , Delphine Casabonne , Nikolaus Becker , Paolo Boffetta , Paul Brennan , Lenka Foretova , Marc Maynadié (2, 3) , James Mckay , Anthony Staines , Kari G. Chaffee , Sara J. Achenbach , Celine M. Vachon , Lynn R. Goldin , Sara S. Strom , Jose F. Leis , J. Brice Weinberg , Neil E. Caporaso , Aaron D. Norman , Anne de Roos , Lindsay M. Morton , Richard K. Severson , Elio Riboli , Paolo Vineis , Rudolph Kaaks , Giovanna Ma , Elisabete Weiderpass , María- Dolores Ma , Roel C. H. Vermeulen , Ruth C. Travis , Melissa C. Southey , Roger L. Milne , Demetrius Albanes , Jarmo Virtamo , Stephanie Weinstein , Jacqueline Clavel , Tongzhang Zheng , Theodore R. Holford , Danylo J. Villano , Ann Ma , John J. Spinelli , Randy D. Gascoyne , Joseph M. Connors , Kimberly A. Bertrand , Edward Giovannucci , Peter Kraft , Anne Kricker , Jenny Turner , Maria Grazia Ma , Giovanni M. Ferri , Lucia Miligi , Liming Liang , Baoshan Ma , Jinyan Huang , Simon Crouch , Ju-Hyun Park , Nilanjan Chatterjee , Kari E. North , John A. Snowden , Josh Wright , Joseph F. Fraumeni , Kenneth Offit , Xifeng Wu , Silvia de Sanjose , James R. Cerhan , Stephen J. Chanock , Nathaniel Rothman , Susan L. Slager (4)

1 NCI-NIH - National Cancer Institute [Bethesda]
2 CEP - Centre d'épidémiologie des populations
3 Registre des hémopathies malignes de Côte d'Or
4 Mayo Clinic [Rochester]

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.

Mots clés: expression; bank1; prioritization; classification; transcription factor eomesodermin; fas gene-mutations; susceptibility loci; follicular lymphoma; risk; variants

Domaines: Hématologie

Sonja I. Berndt, Nicola J. Camp, Christine F. Skibola, Joseph Vijai, Zhaoming Wang, et al.. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nature Communications, 2016, 7, ⟨10.1038/ncomms10933⟩. ⟨hal-01511871⟩