Title |
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
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Published in |
Nature Communications, March 2016
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DOI | 10.1038/ncomms10933 |
Pubmed ID | |
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 |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 5 | 33% |
United Kingdom | 2 | 13% |
India | 1 | 7% |
Austria | 1 | 7% |
Unknown | 6 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 8 | 53% |
Scientists | 5 | 33% |
Practitioners (doctors, other healthcare professionals) | 2 | 13% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Sweden | 1 | <1% |
Brazil | 1 | <1% |
Unknown | 224 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 45 | 20% |
Student > Ph. D. Student | 30 | 13% |
Student > Master | 22 | 10% |
Student > Bachelor | 16 | 7% |
Student > Postgraduate | 15 | 7% |
Other | 40 | 18% |
Unknown | 58 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 50 | 22% |
Biochemistry, Genetics and Molecular Biology | 39 | 17% |
Agricultural and Biological Sciences | 21 | 9% |
Social Sciences | 6 | 3% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 3% |
Other | 36 | 16% |
Unknown | 68 | 30% |