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

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• Alternative Title:
  Nat Commun
• Personal Author:
  Berndt, Sonja I. ; Camp, Nicola J. ; Skibola, Christine F. ; Vijai, Joseph ; Wang, Zhaoming ; Gu, Jian ; Nieters, Alexandra ; Kelly, Rachel S. ; Smedby, Karin E. ; Monnereau, Alain ; Cozen, Wendy ; Cox, Angela ; 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 ; Burdett, Laurie ; 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 ; Link, Brian K. ; Weiner, George J. ; Conde, Lucia ; Bracci, Paige M. ; Riby, Jacques ; Arnett, Donna K. ; Zhi, Degui ; Leach, Justin M. ; Holly, Elizabeth A. ; Jackson, Rebecca D. ; Tinker, Lesley F. ; Benavente, Yolanda ; Sala, Núria ; Casabonne, Delphine ; Becker, Nikolaus ; Boffetta, Paolo ; Brennan, Paul ; Foretova, Lenka ; Maynadie, Marc ; McKay, James ; Staines, Anthony ; Chaffee, Kari G. ; Achenbach, Sara J. ; Vachon, Celine M. ; Goldin, Lynn R. ; Strom, Sara S. ; Leis, Jose F. ; Weinberg, J. Brice ; Caporaso, Neil E. ; Norman, Aaron D. ; De Roos, Anneclaire J. ; Morton, Lindsay M. ; Severson, Richard K. ; Riboli, Elio ; Vineis, Paolo ; Kaaks, Rudolph ; Masala, Giovanna ; Weiderpass, Elisabete ; Chirlaque, María- Dolores ; Vermeulen, Roel C. H. ; Travis, Ruth C. ; Southey, Melissa C. ; Milne, Roger L. ; Albanes, Demetrius ; Virtamo, Jarmo ; Weinstein, Stephanie ; Clavel, Jacqueline ; Zheng, Tongzhang ; Holford, Theodore R. ; Villano, Danylo J. ; Maria, Ann ; Spinelli, John J. ; Gascoyne, Randy D. ; Connors, Joseph M. ; Bertrand, Kimberly A. ; Giovannucci, Edward ; Kraft, Peter ; Kricker, Anne ; Turner, Jenny ; Ennas, Maria Grazia ; Ferri, Giovanni M. ; Miligi, Lucia ; Liang, Liming ; Ma, Baoshan ; Huang, Jinyan ; 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.
• Description:
  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.
• Subjects:
  Adaptor Proteins, Signal Transducing Apoptosis Regulatory Proteins Bcl-2-Like Protein 11 Genetic Predisposition To Disease Genome-Wide Association Study Humans Leukemia, Lymphocytic, Chronic, B-Cell Membrane Proteins Polymorphism, Single Nucleotide Proto-Oncogene Proteins Serpins T-Box Domain Proteins White People

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• Source:
  Nat Commun. 2016; 7.
• Pubmed ID:
  26956414
• Pubmed Central ID:
  PMC4786871
• Document Type:
  Journal Article
• Funding:
  1U58 DP000807-01/DP/NCCDPHP CDC HHS/United States ; 30 CA086862/CA/NCI NIH HHS/United States ; 5R01 CA69669-02/CA/NCI NIH HHS/United States ; A149445/PHS HHS/United States ; CA098122/CA/NCI NIH HHS/United States ; CA098566/CA/NCI NIH HHS/United States ; CA1046282/CA/NCI NIH HHS/United States ; CA118444/CA/NCI NIH HHS/United States ; CA148690/CA/NCI NIH HHS/United States ; CA149445/CA/NCI NIH HHS/United States ; CA154643/CA/NCI NIH HHS/United States ; CA165923/CA/NCI NIH HHS/United States ; CA167552/CA/NCI NIH HHS/United States ; CA186107/CA/NCI NIH HHS/United States ; CA49449/CA/NCI NIH HHS/United States ; CA62006/CA/NCI NIH HHS/United States ; CA87969/CA/NCI NIH HHS/United States ; CA92153/CA/NCI NIH HHS/United States ; ES000260/ES/NIEHS NIH HHS/United States ; HHSN261201000006C/PHS HHS/United States ; HHSN261201000026C/PHS HHS/United States ; HHSN261201000034C/PHS HHS/United States ; HHSN261201000035C/PHS HHS/United States ; HHSN261201000140C/PHS HHS/United States ; HHSN268201100001C/PHS HHS/United States ; HHSN268201100002C/PHS HHS/United States ; HHSN268201100003C/PHS HHS/United States ; HHSN268201100004C/PHS HHS/United States ; HHSN268201100046C/PHS HHS/United States ; HHSN271201100004C/PHS HHS/United States ; K07 CA115687/CA/NCI NIH HHS/United States ; K08CA134919/CA/NCI NIH HHS/United States ; N01-CN-45165/CN/NCI NIH HHS/United States ; N01-PC-65064/PC/NCI NIH HHS/United States ; N01-PC-67008/PC/NCI NIH HHS/United States ; N01-PC-67009/PC/NCI NIH HHS/United States ; N01-PC-67010/PC/NCI NIH HHS/United States ; N01-RC-37004/RC/CCR NIH HHS/United States ; N01-RC-45035/RC/CCR NIH HHS/United States ; N02-PC-71105/PC/NCI NIH HHS/United States ; NIH CA134674/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P30 CA15083/CA/NCI NIH HHS/United States ; P30 CA42014/CA/NCI NIH HHS/United States ; P50 CA97274/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; R01 CA098661/CA/NCI NIH HHS/United States ; R01 CA149445/CA/NCI NIH HHS/United States ; R01 CA92153/CA/NCI NIH HHS/United States ; R35 CA197449/CA/NCI NIH HHS/United States ; U01 HG007033/HG/NHGRI NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; Canadian Institutes of Health Research/Canada ; Cancer Research UK/United Kingdom ; Intramural NIH HHS/United States
• Volume:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:eac9b36e08c610bb1dae406a6df1e821ef795636b1225ddb3bd41c00e8711000
• Download URL:
  https://stacks.cdc.gov/view/cdc/41035/cdc_41035_DS1.pdf
• File Type:
  [PDF - 1.02 MB ]