Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility
OPEN Nature communications | 3 Dec 2017
A Sud, H Thomsen, PJ Law, A Försti, MIDS Filho, A Holroyd, P Broderick, G Orlando, O Lenive, L Wright, R Cooke, D Easton, P Pharoah, A Dunning, J Peto, F Canzian, R Eeles, Z Kote-Jarai, K Muir, N Pashayan, P Hoffmann, MM Nöthen, KH Jöckel, EPV Strandmann, T Lightfoot, E Kane, E Roman, A Lake, D Montgomery, RF Jarrett, AJ Swerdlow, A Engert, N Orr, K Hemminki and RS Houlston
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.
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