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Variable host control of their ongoing abundance (\u201cload\u201d) can lead to clearance or disease\n                  <jats:sup>3\u20135<\/jats:sup>\n                  . We analyzed the viral DNA load of 31 common viruses in human blood and saliva using whole-genome sequencing data from UK Biobank (n=490,401), All of Us (n=414,817), and SPARK (n=12,519). Viral DNA load varied markedly with age, time of day, and season; most viruses were also present at greater abundance in men than in women. Human genetic variation at dozens of loci associated with DNA load of seven viruses: Epstein-Barr virus (EBV, 45 loci), human herpesvirus 7 (HHV-7, 37 loci), HHV-6B, Merkel cell polyomavirus, and three anelloviruses. Variation at the major histocompatibility complex (MHC) locus generated the strongest associations (\n                  <jats:italic>p<\/jats:italic>\n                  = 5.8\u00d710\n                  <jats:sup>\u22129<\/jats:sup>\n                  to 2.5\u00d710\n                  <jats:sup>\u22121459<\/jats:sup>\n                  ), which were specific to each virus. The\n                  <jats:italic>HLA-B*08:01<\/jats:italic>\n                  allele also exhibited a host-virus genetic interaction with EBV subtype (\n                  <jats:italic>p<\/jats:italic>\n                  = 7.4\u00d710\n                  <jats:sup>\u221270<\/jats:sup>\n                  ). Other human genetic effects implicated genes encoding proteins that process peptides for antigen presentation, such as\n                  <jats:italic>ERAP1<\/jats:italic>\n                  (HHV-7,\n                  <jats:italic>p<\/jats:italic>\n                  = 2.7\u00d710\n                  <jats:sup>\u221278<\/jats:sup>\n                  ) and\n                  <jats:italic>ERAP2<\/jats:italic>\n                  (EBV,\n                  <jats:italic>p<\/jats:italic>\n                  = 4.6\u00d710\n                  <jats:sup>\u2212111<\/jats:sup>\n                  ). Mendelian randomization analyses supported a strong causal effect of EBV DNA load on increased risk of Hodgkin lymphoma (\n                  <jats:italic>p<\/jats:italic>\n                  = 1.8\u00d710\n                  <jats:sup>\u22123<\/jats:sup>\n                  ) but not multiple sclerosis (\n                  <jats:italic>p<\/jats:italic>\n                  = 0.52). This suggests that higher chronic EBV load increases lymphoma risk, whereas associations of EBV infection with autoimmune conditions reflect host immune responses to particular viral epitopes.\n                <\/jats:p>","DOI":"10.1101\/2025.09.08.674901","type":"posted-content","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T04:45:34Z","timestamp":1757652334000},"source":"Crossref","is-referenced-by-count":2,"title":["The DNA virome varies with human genes and environments"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-0189","authenticated-orcid":false,"given":"Nolan","family":"Kamitaki","sequence":"first","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Center for Data Sciences, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"},{"name":"Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1174-7700","authenticated-orcid":false,"given":"David","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Center for Data Sciences, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6954-8184","authenticated-orcid":false,"given":"Steven A","family":"McCarroll","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA, USA"},{"name":"Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-9064","authenticated-orcid":false,"given":"Po-Ru","family":"Loh","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Center for Data Sciences, Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026031311501271000_2025.09.08.674901v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00536-5"},{"key":"2026031311501271000_2025.09.08.674901v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.08.026"},{"key":"2026031311501271000_2025.09.08.674901v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70010-5"},{"key":"2026031311501271000_2025.09.08.674901v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80493-8"},{"key":"2026031311501271000_2025.09.08.674901v2.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198912143212401"},{"key":"2026031311501271000_2025.09.08.674901v2.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa023141"},{"key":"2026031311501271000_2025.09.08.674901v2.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"2026031311501271000_2025.09.08.674901v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01167-9"},{"key":"2026031311501271000_2025.09.08.674901v2.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006292"},{"key":"2026031311501271000_2025.09.08.674901v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.016"},{"key":"2026031311501271000_2025.09.08.674901v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2021.02.002"},{"key":"2026031311501271000_2025.09.08.674901v2.12","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2353\/jmoldx.2008.080023","article-title":"Laboratory Assays for Epstein-Barr Virus-Related Disease","volume":"10","year":"2008","journal-title":"J. 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