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

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

doi:10.1038/ncomms14175

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

Published Date:

Feb 06 2017

Publisher's site:

http://dx.doi.org/10.1038/ncomms14175 New Site Icon

Source:

Nat Commun. 2017; 8.

[PDF - 953.20 KB]

Details:

Personal Authors:

Law, Philip J. ; Berndt, Sonja I. ; Speedy, Helen E. ; Camp, Nicola J. ; Sava, Georgina P. ; ... More ▼

Pubmed ID:

28165464

Pubmed Central ID:

PMC5303820

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.

Document Type:

Journal Article

Collection(s):

CDC Public Access

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
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

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