{"doi":"10.1001/jamanetworkopen.2022.25647","title":"Association of Single-Nucleotide Variants in the Human Leukocyte Antigen and Other Loci With Childhood Hodgkin Lymphoma","abstract":"Importance: Studies focusing on genetic susceptibility of childhood Hodgkin lymphoma (HL) are limited. Objectives: To identify genetic variants associated with childhood-onset HL vs adult-onset HL. Design, Setting, and Participants: This genetic association study was performed with 3 cohorts: the St Jude Lifetime Cohort Study (SJLIFE), initiated in 2007 with ongoing follow-up, and the original and expansion cohorts of the Childhood Cancer Survivor Study (CCSS), initiated in the 1990s with ongoing follow-up. Results of these genome-wide association studies (GWASs) were combined via meta-analysis. Data were analyzed from June 2021 to June 2022. Main Outcomes and Measures: Childhood HL was the focused outcome. Single-nucleotide variant (SNV, formerly single-nucleotide polymorphism) array genotyping and imputation were conducted for the CCSS original cohort, and whole-genome sequencing was performed for the SJLIFE and CCSS expansion cohort. Results: A total of 1286 HL cases (mean diagnosis [SD] age, 14.6 [3.9] years), 6193 non-HL childhood cancer cases, and 369 noncancer controls, all of European ancestry, were included in the analysis. Using step-wise conditional logistic regression, the odds ratios (ORs) for each of the 3 independent SNVs identified in the human leukocyte antigen (HLA) locus were 1.80 (95% CI, 1.59-2.03; P = 2.14 × 10-21) for rs28383311, 1.53 (95% CI, 1.37-1.70; P = 2.05 × 10-14) for rs3129198, and 1.51 (95% CI, 1.35-1.69; P = 6.21 × 10-13) for rs3129890. Further HLA imputation revealed 9 alleles and 55 amino acid changes that potentially conferred HL susceptibility. In addition, 5 non-HLA loci were identified: (1) rs1432297 (OR, 1.29; 95% CI, 1.18-1.41; P = 2.5 × 10-8; r2 = 0.55; D' = 0.75 with previously reported rs1432295, REL); (2) rs2757647 (OR, 1.30; 95% CI, 1.18-1.42; P = 3.5 × 10-8; r2 = 0.59; D' = 0.83 with previously reported rs6928977, AHI1); (3) rs13279159 (OR, 1.33; 95% CI, 1.20-1.47; P = 1.7 × 10-8; r2 = 0.75; D' = 1.00 with previously reported rs2019960, PVT1); (4) rs3824662 (OR, 1.52; 95% CI, 1.33-1.73; P = 3.9 × 10-10; r2 = 0.91; D' = 1.00 with previously reported rs3781093, GATA3); and (5) rs117953624 (OR, 1.98; 95% CI, 1.56-2.51; P = 1.5 × 10-8; minor allele frequency, 0.02), a novel uncommon SNV mapped to PDGFD. Twelve of 18 previously reported genome-wide significant non-HLA SNVs (67%) were replicated with statistically significant results. Conclusions and Relevance: In this genetic association study, a predominantly common and potentially unique genetic etiology was found between childhood-onset and adulthood-onset HL.","journal":"JAMA Network Open","year":2022,"id":280859,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8108,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":309087,"name":"Nan Song","orcid":"0000-0002-9182-1060","position":1,"is_corresponding":false},{"id":887271,"name":"Qian Dong","orcid":"0000-0002-2028-9046","position":2,"is_corresponding":false},{"id":887273,"name":"Xiaojun Sun","orcid":"0000-0001-7283-0175","position":3,"is_corresponding":false},{"id":252145,"name":"Heather L. Mulder","orcid":"0000-0003-2024-9498","position":4,"is_corresponding":false},{"id":5544,"name":"John Easton","orcid":"0000-0003-4503-6608","position":5,"is_corresponding":false},{"id":1812,"name":"Jinghui Zhang","orcid":"0000-0003-3350-9682","position":6,"is_corresponding":false},{"id":255628,"name":"Yutaka Yasui","orcid":"0000-0002-7717-8638","position":7,"is_corresponding":false},{"id":262392,"name":"Smita Bhatia","orcid":"0000-0002-7755-5683","position":8,"is_corresponding":false},{"id":230934,"name":"Gregory T. Armstrong","orcid":"0000-0001-8722-4207","position":9,"is_corresponding":false},{"id":955680,"name":"Hui Wang","orcid":"0000-0001-8727-9830","position":10,"is_corresponding":false},{"id":255612,"name":"Kirsten K. Ness","orcid":"0000-0002-2084-1507","position":11,"is_corresponding":false},{"id":255630,"name":"Melissa M. Hudson","orcid":"0000-0001-6984-2407","position":12,"is_corresponding":false},{"id":230935,"name":"Leslie L. Robison","orcid":"0000-0001-7460-8578","position":13,"is_corresponding":false},{"id":255626,"name":"Zhaoming Wang","orcid":"0000-0001-7556-3869","position":14,"is_corresponding":false},{"id":955679,"name":"Cheng Chen","orcid":"0000-0001-9773-2993","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:07.472902Z","pmid":"35939300","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}