Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility
Easton D.; Brenner H.; Pashayan N.; Batra J.; Travis R.; Nöthen M.; Olama A.; Menegaux F.; Dominguez M.; Lenive O.; Wright L.; Park J.; Sud A.; Wiklund F.; Holroyd A.; Kane E.; Albanes D.; Houlston R.; Neuhausen S.; Schleutker J.; Peto J.; Nordestgaard B.; Strandmann E.; John E.; Giles G.; Wolk A.; Engert A.; Stevens V.; Townsend P.; Teixeira M.; Kogevinas M.; Cybulski C.; Roman E.; Orr N.; Vega A.; Law P.; Koutros S.; Mucci L.; Ingles S.; Thomsen H.; Swerdlow A.; Filho M.; Kibel A.; Henderson B.; Kim J.; Penney K.; Lessel D.; Gronberg H.; Lightfoot T.; Newcomb L.; Clements J.; Neal D.; Kote-Jarai Z.; Jarrett R.; Muir K.; Schumacher F.; Berndt S.; Eeles R.; Cancel-Tassin G.; Maehle L.; De Ruyck K.; Weinstein S.; Broderick P.; Maier C.; Claessens F.; Roobol M.; Lake A.; Tangen C.; Orlando G.; Rosenstein B.; Chanock S.; Lu Y.; Cooke R.; Jöckel K.; Hemminki K.; Dunning A.; Canzian F.; Usmani N.; Benlloch S.; Sorensen K.; Haiman C.; Hoffmann P.; Pharoah P.; Försti A.; Razack A.; Montgomery D.; Conti D.; West C.; Stanford J.; Hamilton R.; Kaneva R.
https://urn.fi/URN:NBN:fi-fe2021042717830
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]