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

• Published in: Nature communications 2016-03, Vol.7 (1), p.10933-9, Article 10933
• Main Authors: Berndt, Sonja I., Skibola, Christine F., Vijai, Joseph, Wang, Zhaoming, Kelly, Rachel S., Smedby, Karin E., Cozen, Wendy, Wang, Sophia S., Lan, Qing, Teras, Lauren R., Machado, Moara, Yeager, Meredith, Brooks-Wilson, Angela R., Hartge, Patricia, Purdue, Mark P., Birmann, Brenda M., Vajdic, Claire M., Cocco, Pierluigi, Zhang, Yawei, Giles, Graham G., Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Montalvan, Rebecca, Hutchinson, Amy, Ye, Yuanqing, Call, Timothy G., Shanafelt, Tait D., Novak, Anne J., Kay, Neil E., Liebow, Mark, Cunningham, Julie M., Allmer, Cristine, Hjalgrim, Henrik, Adami, Hans-Olov, Melbye, Mads, Glimelius, Bengt, Chang, Ellen T., Glenn, Martha, Curtin, Karen, Cannon-Albright, Lisa A., Diver, W Ryan, Weiner, George J., Conde, Lucia, Bracci, Paige M., Riby, Jacques, Arnett, Donna K., Leach, Justin M., Holly, Elizabeth A., Benavente, Yolanda, Sala, Núria, Casabonne, Delphine, Becker, Nikolaus, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Chaffee, Kari G., Achenbach, Sara J., Strom, Sara S., Leis, Jose F., Caporaso, Neil E., De Roos, Anneclaire J., Severson, Richard K., Kaaks, Rudolph, Weiderpass, Elisabete, Chirlaque, María- Dolores, Vermeulen, Roel C. H., Travis, Ruth C., Southey, Melissa C., Milne, Roger L., Albanes, Demetrius, Zheng, Tongzhang, Holford, Theodore R., Maria, Ann, Gascoyne, Randy D., Connors, Joseph M., Bertrand, Kimberly A., Giovannucci, Edward, Kraft, Peter, Kricker, Anne, Turner, Jenny, Ennas, Maria Grazia, Miligi, Lucia, Liang, Liming, Ma, Baoshan, Crouch, Simon, Park, Ju-Hyun, Chatterjee, Nilanjan, North, Kari E., Snowden, John A., Wright, Josh, Fraumeni, Joseph F., Offit, Kenneth, Wu, Xifeng, de Sanjose, Silvia, Cerhan, James R., Chanock, Stephen J., Rothman, Nathaniel, Slager, Susan L.
• Format: Article
• Language: English
• Subjects: 631/208/205/2138; 631/208/68; 631/67/1990/283/1895; 631/80/82/23; Adaptor Proteins, Signal Transducing - genetics; Agent Orange; Apoptosis; Apoptosis Regulatory Proteins - genetics; Bcl-2-Like Protein 11; Chromosome 2; Chromosome 3; Chromosome 4; Chronic lymphocytic leukemia; Community medicine, Social medicine: 801; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health sciences: 800; Helsefag: 800; Hematology; Heritability; Human health and pathology; Humanities and Social Sciences; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Life Sciences; Loci; Lymphatic leukemia; Malignancy; Medical disciplines: 700; Medicin och hälsovetenskap; Medisinske Fag: 700; Membrane Proteins - genetics; Meta-analysis; multidisciplinary; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins - genetics; Samfunnsmedisin, sosialmedisin: 801; Science; Science (multidisciplinary); Serpins - genetics; Single-nucleotide polymorphism; T-Box Domain Proteins - genetics; VDP; White People - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10933

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