Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
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Published Date:Feb 06 2017
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Source:Nat Commun. 2017; 8.
Details:
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Personal Authors:
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Keywords:
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Pubmed ID:28165464
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Pubmed Central ID:PMC5303820
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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.
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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
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Supporting Files:
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