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Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.

Amit SudHauke ThomsenPhilip J LawAsta FörstiMiguel Inacio da Silva FilhoAmy HolroydPeter BroderickGiulia OrlandoOleg LeniveLauren WrightRosie CookeDouglas EastonPaul David Peter PharoahAlison DunningJulian PetoFederico CanzianRosalind A EelesZSofia Kote-JaraiKenneth Ross MuirNora Pashayannull nullPer HoffmannMarkus M NöthenKarl-Heinz JöckelElke Pogge von StrandmannTracy LightfootEleanor KaneEve RomanAnnette LakeDorothy MontgomeryRuth F JarrettAnthony J SwerdlowAndreas EngertNick OrrKari HemminkiRichard S Houlston
Published in: Nature communications (2017)
Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10-8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10-17), 6q23.3 (rs6928977, P = 4.62 × 10-11), 10p14 (rs3781093, P = 9.49 × 10-13), 13q34 (rs112998813, P = 4.58 × 10-8) and 16p13.13 (rs34972832, P = 2.12 × 10-8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
Keyphrases
  • hodgkin lymphoma
  • genome wide association study
  • genome wide association
  • genome wide
  • transcription factor
  • immune response
  • gene expression
  • dna methylation
  • dna damage
  • dendritic cells
  • dna binding