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However, whether human leukocyte antigen (<jats:italic>HLA<\/jats:italic>) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. <jats:italic>HLA<\/jats:italic> alleles are imputed with accuracy &gt;90% for <jats:italic>HLA<\/jats:italic> class I and 85-89% for class II alleles. BL risk is elevated with <jats:italic>HLA-DQA1*04:01<\/jats:italic> (adjusted odds ratio [OR]\u2009=\u20091.61, 95% confidence interval [CI]\u2009=\u20091.32-1.97, <jats:italic>P<\/jats:italic>\u2009=\u20093.71\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>), with rs2040406(G) in <jats:italic>HLA-DQA1<\/jats:italic> region (OR\u2009=\u20091.43, 95% CI\u2009=\u20091.26-1.63, <jats:italic>P<\/jats:italic>\u2009=\u20094.62\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>), and with amino acid Gln at position 53 versus other variants in <jats:italic>HLA-DQA1<\/jats:italic> (OR\u2009=\u20091.36, <jats:italic>P<\/jats:italic>\u2009=\u20092.06\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>). The associations with <jats:italic>HLA-DQA1*04:01<\/jats:italic> (OR\u2009=\u20091.29, <jats:italic>P<\/jats:italic>\u2009=\u20090.03) and rs2040406(G) (OR\u2009=\u20091.68, <jats:italic>P<\/jats:italic>\u2009=\u20090.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased <jats:italic>HLA-DQB1<\/jats:italic> expression in eQTLs in EBV transformed lymphocytes. Our results support the role of <jats:italic>HLA<\/jats:italic> variation in the etiology of BL and suggest that a promising area of research might be understanding the link between <jats:italic>HLA<\/jats:italic> variation and EBV control.<\/jats:p>","DOI":"10.1038\/s42003-023-05701-5","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T20:02:06Z","timestamp":1704484926000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-651X","authenticated-orcid":false,"given":"Zhiwei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-6166","authenticated-orcid":false,"given":"Yang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Kirimunda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murielle","family":"Verboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-2380","authenticated-orcid":false,"given":"Olusegun 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