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

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 x 10(-8)) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 x 10(-17)), 6q23.3 (rs6928977, P = 4.62 x 10(-11)), 10p14 (rs3781093, P = 9.49 x 10(-13)), 13q34 (rs112998813, P = 4.58 x 10(-8)) and 16p13.13 (rs34972832, P= 2.12 x 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 HLADRB1). 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.