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

Philip J Law , Sonja I Berndt (1) , Helen Speedy , Nicola J Camp , Georgina P Sava , Chris Skibola , Amy Holroyd (2) , Vijai Joseph (3) , Nicola J. Sunter , Alexandra Nieters , Silvia Bea , Alain Monnereau , David Martin-Garcia , Lynn R Goldin , Guillem Clot (4) , Lauren R Teras , Inés Quintela , Brenda M Birmann , Sandrine Jayne , Wendy Cozen , Aneela Majid (5) , Karin E Smedby , Qing Lan , Claire Dearden , Angel Brooks-Wilson , Andrew G. Hall (6) , Mark Purdue , Tryfonia Mainou-Fowler , Claire M Vajdic , Graham H Jackson (7) , Pierluigi Cocco , Helen Marr , Yawei Zhang (8) , Tongzhang Zheng , Graham G Giles (9) , Charles Lawrence (10) , Timothy G Call , Mark Liebow , Mads Melbye , Bengt Glimelius , Larry Mansouri (11) , Martha Glenn (12) , Karen Curtin , W Ryan Diver , Brian K Link (13) , Lucia Conde , Paige M Bracci , Elizabeth A Holly , Rebecca D Jackson , Lesley F Tinker , Yolanda Benavente , Paolo Boffetta , Paul Brennan , Marc Maynadié (14) , James Mckay , Demetrius Albanes , Stephanie Weinstein , Zhaoming Wang , Neil E Caporaso , Lindsay M Morton , Richard Severson , Elio Riboli , Paolo Vineis , Roel C H Vermeulen , Melissa C Southey , Roger L Milne , Jacqueline Clavel (15) , Sabine Topka , John J Spinelli , Peter Kraft , Maria Grazia Ennas (16) , Geoffrey Summerfield , Giovanni M Ferri , Robert J Harris (17) , Lucia Miligi , Andrew R Pettitt , Kari E North , David J Allsup , Joseph F Fraumeni , James R Bailey (18) , Kenneth Offit , Guy Pratt (19) , Henrik Hjalgrim , Chris Pepper (20) , Stephen J Chanock , Chris Fegan , Richard Rosenquist (11) , Silvia de Sanjose , Ángel Carracedo (21) , Martin J S Dyer (22) , Daniel Catovsky (23) , Elias Campo , James R Cerhan (24) , James M Allan (25) , Nathanial Rothman , Richard Houlston (26) , Susan Slager (24)

1 NCI-NIH - National Cancer Institute [Bethesda]
2 Microsoft Research [Redmond]
3 Department of Physics, Loyola College, Nungambakkam, Chennai – 600 034
4 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
5 University of Aleppo [Aleppo]
6 SMRU - Sea Mammal Research Unit [University of St Andrews]
7 Department of Chemical Engineering
8 MONARIS - De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies
9 The Cancer Council Victoria
10 University of Oulu
11 Uppsala Universitet [Uppsala]
12 UPN - Université Paris Nanterre
13 University of Iowa [Iowa City]
14 Registre des hémopathies malignes de Côte d'Or
15 IRSN - Institut de Radioprotection et de Sûreté Nucléaire
16 B.B. Brodie Department of Neuroscience
17 Penn State - Pennsylvania State University
18 UoN - University of Newcastle [Australia]
19 AIM (UMR_7158 / UMR_E_9005 / UM_112) - Astrophysique Interprétation Modélisation
20 Department of Haematology, School of Medicine
21 CIBER de Enfermedades Raras (CIBERER)
22 University of Leeds
23 Haemato-oncology
24 Mayo Clinic [Rochester]
25 NICR - Northern Institute for Cancer Research [Newcastle]
26 Institute of Cancer Research, Belmont, Sutton

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.

Domaines: Sciences du Vivant [q-bio]; Autre [q-bio.OT]

Philip J Law, Sonja I Berndt, Helen Speedy, Nicola J Camp, Georgina P Sava, et al.. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.. Nature Communications, 2017, 8, pp.14175. ⟨10.1038/ncomms14175⟩. ⟨hal-01545767⟩