Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.
Amit SudHauke ThomsenGiulia OrlandoAsta FörstiPhilip J LawPeter BroderickRosie CookeFadi HaririTomi PastinenDouglas F EastonPaul David Peter PharoahAlison M DunningJulian PetoFrederico CanzianRosalind A EelesZSofia Kote-JaraiKenneth MuirNora PashayanDaniele Campanull nullPer HoffmannMarkus Maria NöthenKarl-Heinz JöckelElke Pogge von StrandmannAnthony J SwerdlowNicholas OrrAndreas EngertKari HemminkiRichard S HoulstonPublished in: Blood (2018)
To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of 7 genome-wide association studies totaling 5325 HL cases and 22 423 control patients. We identify 5 new HL risk loci at 6p21.31 (rs649775; P = 2.11 × 10-10), 6q23.3 (rs1002658; P = 2.97 × 10-8), 11q23.1 (rs7111520; P = 1.44 × 10-11), 16p11.2 (rs6565176; P = 4.00 × 10-8), and 20q13.12 (rs2425752; P = 2.01 × 10-8). Integration of gene expression, histone modification, and in situ promoter capture Hi-C data at the 5 new and 13 known risk loci implicates dysfunction of the germinal center reaction, disrupted T-cell differentiation and function, and constitutive NF-κB activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.
Keyphrases
- hodgkin lymphoma
- genome wide association study
- genome wide association
- gene expression
- dna methylation
- genome wide
- end stage renal disease
- oxidative stress
- newly diagnosed
- chronic kidney disease
- electronic health record
- big data
- peritoneal dialysis
- signaling pathway
- transcription factor
- prognostic factors
- immune response
- lps induced
- data analysis
- copy number
- cell proliferation
- artificial intelligence
- resting state
- functional connectivity