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

Authors:
Sonja I Berndt 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 Machado Meredith Yeager Angela R Brooks-Wilson Patricia Hartge Mark P Purdue 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 J Novak Neil E Kay Mark Liebow Julie M Cunningham Cristine Allmer Henrik Hjalgrim Hans-Olov Adami Mads Melbye Bengt Glimelius Ellen T Chang Martha Glenn 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 Maynadie 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 Anneclaire J De Roos Lindsay M Morton Richard K Severson Elio Riboli Paolo Vineis Rudolph Kaaks Giovanna Masala Elisabete Weiderpass María-Dolores Chirlaque 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 Maria John J Spinelli Randy D Gascoyne Joseph M Connors Kimberly A Bertrand Edward Giovannucci Peter Kraft Anne Kricker Jenny Turner Maria Grazia Ennas 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

Nat Commun 2016 Mar 9;7:10933. Epub 2016 Mar 9.

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.

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.

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http://dx.doi.org/10.1038/ncomms10933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786871PMC
March 2016
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