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

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

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.

OriginalsprogEngelsk
Artikelnummer14175
TidsskriftNature Communications
Vol/bind8
ISSN2041-1723
DOI
StatusUdgivet - 2017

ID: 258839725