Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

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• Alternative Title:
  Nat Commun
• Personal Author:
  Law, Philip J. ; Berndt, Sonja I. ; Speedy, Helen E. ; Camp, Nicola J. ; Sava, Georgina P. ; Skibola, Christine F. ; Holroyd, Amy ; Joseph, Vijai ; Sunter, Nicola J. ; Nieters, Alexandra ; Bea, Silvia ; Monnereau, Alain ; Martin-Garcia, David ; Goldin, Lynn R. ; Clot, Guillem ; Teras, Lauren R. ; Quintela, Inés ; Birmann, Brenda M. ; Jayne, Sandrine ; Cozen, Wendy ; Majid, Aneela ; Smedby, Karin E. ; Lan, Qing ; Dearden, Claire ; Brooks-Wilson, Angela R. ; Hall, Andrew G. ; Purdue, Mark P. ; Mainou-Fowler, Tryfonia ; Vajdic, Claire M. ; Jackson, Graham H. ; Cocco, Pierluigi ; Marr, Helen ; Zhang, Yawei ; Zheng, Tongzhang ; Giles, Graham G. ; Lawrence, Charles ; Call, Timothy G. ; Liebow, Mark ; Melbye, Mads ; Glimelius, Bengt ; Mansouri, Larry ; Glenn, Martha ; Curtin, Karen ; Diver, W Ryan ; Link, Brian K. ; Conde, Lucia ; Bracci, Paige M. ; Holly, Elizabeth A. ; Jackson, Rebecca D. ; Tinker, Lesley F. ; Benavente, Yolanda ; Boffetta, Paolo ; Brennan, Paul ; Maynadie, Marc ; McKay, James ; Albanes, Demetrius ; Weinstein, Stephanie ; Wang, Zhaoming ; Caporaso, Neil E. ; Morton, Lindsay M. ; Severson, Richard K. ; Riboli, Elio ; Vineis, Paolo ; Vermeulen, Roel C. H. ; Southey, Melissa C. ; Milne, Roger L. ; Clavel, Jacqueline ; Topka, Sabine ; Spinelli, John J. ; Kraft, Peter ; Ennas, Maria Grazia ; Summerfield, Geoffrey ; Ferri, Giovanni M. ; Harris, Robert J. ; Miligi, Lucia ; Pettitt, Andrew R. ; North, Kari E. ; Allsup, David J. ; Fraumeni, Joseph F. ; Bailey, James R. ; Offit, Kenneth ; Pratt, Guy ; Hjalgrim, Henrik ; Pepper, Chris ; Chanock, Stephen J. ; Fegan, Chris ; Rosenquist, Richard ; de Sanjose, Silvia ; Carracedo, Angel ; Dyer, Martin J. S. ; Catovsky, Daniel ; Campo, Elias ; Cerhan, James R. ; Allan, James M. ; Rothman, Nathanial ; Houlston, Richard ; Slager, Susan
• Description:
  Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10(-13)), 1q42.13 (rs41271473, P=1.06 × 10(-10)), 4q24 (rs71597109, P=1.37 × 10(-10)), 4q35.1 (rs57214277, P=3.69 × 10(-8)), 6p21.31 (rs3800461, P=1.97 × 10(-8)), 11q23.2 (rs61904987, P=2.64 × 10(-11)), 18q21.1 (rs1036935, P=3.27 × 10(-8)), 19p13.3 (rs7254272, P=4.67 × 10(-8)) and 22q13.33 (rs140522, P=2.70 × 10(-9)). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
• Subjects:
  Adult Antibody Formation B-Lymphocytes Case-Control Studies Chromosome Mapping Chromosomes, Human Female Genetic Predisposition To Disease Genome-Wide Association Study Humans Leukemia, Lymphocytic, Chronic, B-Cell Male Middle Aged Polymorphism, Single Nucleotide Young Adult

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• Source:
  Nat Commun. 2017; 8.
• Pubmed ID:
  28165464
• Pubmed Central ID:
  PMC5303820
• Document Type:
  Journal Article
• Funding:
  N01 PC067009/CN/NCI NIH HHS/United States ; HHSN268201100001I/HL/NHLBI NIH HHS/United States ; HHSN261201000035C/PC,CA/None/None ; P30 CA016087/CA/NCI NIH HHS/United States ; HHSN261201000140C/CA/NCI NIH HHS/United States ; N01 PC067010/PC/NCI NIH HHS/United States ; R01 CA098122/CA/NCI NIH HHS/United States ; U01 HG007033/HG/NHGRI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; HHSN261201000006C/CP/NCI NIH HHS/United States ; R21 CA165923/CA/NCI NIH HHS/United States ; HHSN268201100004I/HL/NHLBI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R21 CA178800/CA/NCI NIH HHS/United States ; HHSN268201100046C/HL/NHLBI NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; N01 PC067008/PC/NCI NIH HHS/United States ; HHSN268201100003C/WH/WHI NIH HHS/United States ; R01 CA148690/CA/NCI NIH HHS/United States ; P30 ES000260/ES/NIEHS NIH HHS/United States ; U58 DP000807/DP/NCCDPHP CDC HHS/United States ; R01 CA154643/CA/NCI NIH HHS/United States ; R01 CA062006/CA/NCI NIH HHS/United States ; N01 PC065064/PC/NCI NIH HHS/United States ; K08 CA134919/CA/NCI NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; HHSN271201100004C/AG/NIA NIH HHS/United States ; R01 CA098661/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; HHSN268201100002C/WH/WHI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 CA092153/CA/NCI NIH HHS/United States ; HHSN261201000035I/CA/NCI NIH HHS/United States ; HHSN261201000034C/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; N01RC37004/RC/CCR NIH HHS/United States ; R01 CA087014/CA/NCI NIH HHS/United States ; P50 CA097274/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; HHSN268201100002I/HL/NHLBI NIH HHS/United States ; KL2 TR001862/TR/NCATS NIH HHS/United States ; N01CO12400/CA/NCI NIH HHS/United States ; N01 CN045165/CN/NCI NIH HHS/United States ; U01 CA049449/CA/NCI NIH HHS/United States ; R01 CA149445/CA/NCI NIH HHS/United States ; R01 CA134674/CA/NCI NIH HHS/United States ; R01 CA045614/CA/NCI NIH HHS/United States ; HHSN261201000026C/CA/NCI NIH HHS/United States ; HHSN268201100001C/WH/WHI NIH HHS/United States ; HHSN268201100004C/WH/WHI NIH HHS/United States ; U01 CA118444/CA/NCI NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; R03 CA089745/CA/NCI NIH HHS/United States
• Volume:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:fe5fd98c1025e11cc26e600339fea6fa6f371a72ffc5633e8865dbbfa627cf4a
• Download URL:
  https://stacks.cdc.gov/view/cdc/44615/cdc_44615_DS1.pdf
• File Type:
  [PDF - 953.20 KB ]