Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Sonja I. Berndt, Christine F. Skibola, Vijai Joseph, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, Alain Monnereau, Sophia S. Wang, Rachel S. Kelly, Qing Lan, Lauren R. Teras, Nilanjan Chatterjee, Charles C. Chung, Meredith Yeager, Angela R. Brooks-Wilson, Patricia Hartge, Mark P. Purdue, Brenda M. Birmann, Bruce K. ArmstrongPierluigi Cocco, Yawei Zhang, Gianluca Severi, Anne Zeleniuch-Jacquotte, Charles Lawrence, Laurie Burdette, Jeffrey Yuenger, Amy Hutchinson, Kevin B. Jacobs, Timothy G. Call, Tait D. Shanafelt, Anne J. Novak, Neil E. Kay, Mark Liebow, Alice H. Wang, Karin E. Smedby, Hans Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T. Chang, Martha Glenn, Karen Curtin, Lisa A. Cannon-Albright, Brandt Jones, W. Ryan Diver, Brian K. Link, George J. Weiner, Lucia Conde, Paige M. Bracci, Jacques Riby, Elizabeth A. Holly, Martyn T. Smith, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, James McKay, Anthony Staines, Kari G. Rabe, Sara J. Achenbach, Celine M. Vachon, Lynn R. Goldin, Sara S. Strom, Mark C. Lanasa, Logan G. Spector, Jose F. Leis, Julie M. Cunningham, J. Brice Weinberg, Vicki A. Morrison, Neil E. Caporaso, Aaron D. Norman, Martha S. Linet, Anneclaire J. De Roos, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Giovanna Masala, Elisabete Weiderpass, María Dolores Chirlaque, Roel C.H. Vermeulen, Ruth C. Travis, Graham G. Giles, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R. Holford, Kenneth Offit, Andrew Zelenetz, Robert J. Klein, John J. Spinelli, Kimberly A. Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Claire M. Vajdic, Maria Grazia Ennas, Giovanni M. Ferri, Lucia Miligi, Liming Liang, Joshua Sampson, Simon Crouch, Ju Hyun Park, Kari E. North, Angela Cox, John A. Snowden, Josh Wright, Angel Carracedo, Carlos Lopez-Otin, Silvia Bea, Itziar Salaverria, David Martin-Garcia, Elias Campo, Joseph F. Fraumeni, Silvia De Sanjose, Henrik Hjalgrim, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

Original languageEnglish (US)
Pages (from-to)868-876
Number of pages9
JournalNature Genetics
Volume45
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Genetics

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