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

Lookup NU author(s): Dr Nicola Sunter, Dr Andrew Hall, Dr Tryfonia Mainou-Fowler, Professor Graham Jackson, Dr Helen Marr, Professor James Allan

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 X 10 (-) (13)), 1q42.13 (rs41271473, P = 1.06 X 10 (-) (10)), 4q24 (rs71597109, P = 1.37 X 10 (-) (10)), 4q35.1 (rs57214277, P = 3.69 X 10 (-) (8)), 6p21.31 (rs3800461, P = 1.97 X 10 (-) (8)), 11q23.2 (rs61904987, P = 2.64 X 10 (-) (11)), 18q21.1 (rs1036935, P = 3.27 X 10 (-) (8)), 19p13.3 (rs7254272, P = 4.67 X 10 (-) (8)) and 22q13.33 (rs140522, P = 2.70 X 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.


Publication metadata

Author(s): 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 YW, Zheng TZ, 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 ZM, 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 SL

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2017

Volume: 8

Online publication date: 06/02/2017

Acceptance date: 06/12/2016

Date deposited: 29/03/2017

ISSN (print): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms14175

DOI: 10.1038/ncomms14175


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Funding

Funder referenceFunder name
American Cancer Society
Association de Recherche Contre le Cancer
Cancer Council Victoria
Centers for Disease Control and Prevention National Program of Cancer Registries
Fondation de France
Institute of Cancer Research
intramural programme of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health
Intramural Research Program of the National Cancer Institute
Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics
Intramural Research Program of the NIH
University of Sydney Faculty of Medicine
University of Utah
Arbib Fund
Bernstein Family Fund for Leukemia and Lymphoma Research
Cancer Council NSW
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS
Leukemia and Lymphoma Society Career Development Award
National Cancer Institute
National Cancer Institute Surveillance Epidemiology and End Results program
Utah State Department of Health
VicHealth
00209805MH CZ-DRO (MMCI)
051210Marato de TV3 Foundation
006438EPIC-Coordinated Action
02 6661Swedish Cancer Society
076113Wellcome Trust
103885California Department of Health Services
11855Italian GxE-Italian Association for Cancer Research (AIRC)
1U58 DP000807-01Centers for Disease Control and Prevention's National Program of Cancer Registries
2014SRG756Agencia de Gestiod AjutsUniversitarisi de Recerca-Generalitat de Catalunya
251553Australian NHMRC
504711Australian NHMRC
209057Australian NHMRC
74419Barbara K. Lipman Lymphoma Research Fund
990920Australian National Health and Medical Research Council
CA1046282NCI, National Institutes of Health
CA149445National Institutes of Health
CA154643NCI, National Institutes of Health
CA167552National Institutes of Health
CA49449National Institutes of Health
CA87969National Institutes of Health
CA89745NCI, National Institutes of Health
CIBERESPSpanish Ministry of Health
CZ.1.05/2.1.00/03.0101RECAMO
DJCLS-R12/23Jose Carreras Leukemia Foundation
C1298/A8362Cancer Research UK (Bobby Moore Fund)
CA098122National Institutes of Health
CA186107National Institutes of Health
CA45614NCI, National Institutes of Health
CA87014NCI, National Institutes of Health
FIS PI13/01136Spanish Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III
FOOD-CT-2006-023103EpiLymph-European Commission
HHSN261201000006CU.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services
HHSN261201000026CNIH from the National Cancer Institute SEER Program
HHSN261201000034CNational Cancer Institute's Surveillance, Epidemiology and End Results Program
HHSN261201000140CNational Cancer Institute's Surveillance, Epidemiology and End Results Program
HHSN268201100003CNational Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
HHSN268201100004CNational Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
HHSN268201100046CNational Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
LRF05001United Kingdom, Bloodwise
N01 CN 45165U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services
N01 RC 37004U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services
N01 RC 45035U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services
HHSN261201000035CNational Cancer Institute's Surveillance, Epidemiology and End Results Program
HHSN268201100001CNational Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
HHSN268201100002CNational Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
N01-PC-65064NCI-SEER-Intramural Research Program of the National Cancer Institute, National Institutes of Health and Public Health Service
N01-PC-67008NCI-SEER-Intramural Research Program of the National Cancer Institute, National Institutes of Health and Public Health Service
N01-PC-67010NCI-SEER-Intramural Research Program of the National Cancer Institute, National Institutes of Health and Public Health Service
HHSN271201100004CNational Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
K08CA134919National Institutes of Health
NO1-CO-12400NIH
LRF06002United Kingdom, Bloodwise
LRF13044United Kingdom, Bloodwise
P30 CA42014HCI Comprehensive Cancer Center Support grant
P50 CA97274Iowa-Mayo SPORE-NCI Specialized Programs of Research Excellence (SPORE) in Human Cancer
PI11/01810Spanish Ministry of Health
PI14/01219Spanish Ministry of Health
N01-PC-67009NCI-SEER-Intramural Research Program of the National Cancer Institute, National Institutes of Health and Public Health Service
N02-PC-71105NCI-SEER-Intramural Research Program of the National Cancer Institute, National Institutes of Health and Public Health Service
RTICESP C03/10Spanish Ministry of Health
SP23-CT-2005-006438EPIC-Coordinated Action
QLK4-CT-2000-00422EpiLymph-European Commission
UL1 TR000135National Center for Advancing Translational Science
RCESP C03/09Spanish Ministry of Health
RTIC RD06/0020/0095Spanish Ministry of Health
StSch4261Federal Office for Radiation Protection
StSch4420Federal Office for Radiation Protection

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