Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.
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ICR Authors
Authors
Law, PJ
Berndt, SI
Speedy, HE
Camp, NJ
Sava, GP
Skibola, CF
Holroyd, A
Joseph, V
Sunter, NJ
Nieters, A
Bea, S
Monnereau, A
Martin-Garcia, D
Goldin, LR
Clot, G
Teras, LR
Quintela, I
Birmann, BM
Jayne, S
Cozen, W
Majid, A
Smedby, KE
Lan, Q
Dearden, C
Brooks-Wilson, AR
Hall, AG
Purdue, MP
Mainou-Fowler, T
Vajdic, CM
Jackson, GH
Cocco, P
Marr, H
Zhang, Y
Zheng, T
Giles, GG
Lawrence, C
Call, TG
Liebow, M
Melbye, M
Glimelius, B
Mansouri, L
Glenn, M
Curtin, K
Diver, WR
Link, BK
Conde, L
Bracci, PM
Holly, EA
Jackson, RD
Tinker, LF
Benavente, Y
Boffetta, P
Brennan, P
Maynadie, M
McKay, J
Albanes, D
Weinstein, S
Wang, Z
Caporaso, NE
Morton, LM
Severson, RK
Riboli, E
Vineis, P
Vermeulen, RCH
Southey, MC
Milne, RL
Clavel, J
Topka, S
Spinelli, JJ
Kraft, P
Ennas, MG
Summerfield, G
Ferri, GM
Harris, RJ
Miligi, L
Pettitt, AR
North, KE
Allsup, DJ
Fraumeni, JF
Bailey, JR
Offit, K
Pratt, G
Hjalgrim, H
Pepper, C
Chanock, SJ
Fegan, C
Rosenquist, R
de Sanjose, S
Carracedo, A
Dyer, MJS
Catovsky, D
Campo, E
Cerhan, JR
Allan, JM
Rothman, N
Houlston, R
Slager, S
Berndt, SI
Speedy, HE
Camp, NJ
Sava, GP
Skibola, CF
Holroyd, A
Joseph, V
Sunter, NJ
Nieters, A
Bea, S
Monnereau, A
Martin-Garcia, D
Goldin, LR
Clot, G
Teras, LR
Quintela, I
Birmann, BM
Jayne, S
Cozen, W
Majid, A
Smedby, KE
Lan, Q
Dearden, C
Brooks-Wilson, AR
Hall, AG
Purdue, MP
Mainou-Fowler, T
Vajdic, CM
Jackson, GH
Cocco, P
Marr, H
Zhang, Y
Zheng, T
Giles, GG
Lawrence, C
Call, TG
Liebow, M
Melbye, M
Glimelius, B
Mansouri, L
Glenn, M
Curtin, K
Diver, WR
Link, BK
Conde, L
Bracci, PM
Holly, EA
Jackson, RD
Tinker, LF
Benavente, Y
Boffetta, P
Brennan, P
Maynadie, M
McKay, J
Albanes, D
Weinstein, S
Wang, Z
Caporaso, NE
Morton, LM
Severson, RK
Riboli, E
Vineis, P
Vermeulen, RCH
Southey, MC
Milne, RL
Clavel, J
Topka, S
Spinelli, JJ
Kraft, P
Ennas, MG
Summerfield, G
Ferri, GM
Harris, RJ
Miligi, L
Pettitt, AR
North, KE
Allsup, DJ
Fraumeni, JF
Bailey, JR
Offit, K
Pratt, G
Hjalgrim, H
Pepper, C
Chanock, SJ
Fegan, C
Rosenquist, R
de Sanjose, S
Carracedo, A
Dyer, MJS
Catovsky, D
Campo, E
Cerhan, JR
Allan, JM
Rothman, N
Houlston, R
Slager, S
Document Type
Journal Article
Date
2017-02-06
Date Accepted
2016-12-06
Abstract
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.
Citation
Nature communications, 2017, 8 pp. 14175 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Cancer Genomics
Molecular & Population Genetics
Molecular & Population Genetics