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

Abstract

<p>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<i>, P</i> = 1.52 × 10−8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, <i>P</i> = 9.43 × 10−17), 6q23.3 (rs6928977, <i>P</i> = 4.62 × 10−11), 10p14 (rs3781093, <i>P</i> = 9.49 × 10−13), 13q34 (rs112998813, <i>P</i> = 4.58 × 10−8) and 16p13.13 (rs34972832<i>, P</i> = 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.<br /></p>