{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:55:24Z","timestamp":1768550124640,"version":"3.49.0"},"posted":{"date-parts":[[2020,5,7]]},"group-title":"Genetic and Genomic Medicine","reference-count":103,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,9,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and therapeutic opportunities.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a comprehensive study including genome-wide and transcriptome-wide association analyses to identify genetic loci associated with immunoglobulin G antibody response to 28 antigens for 16 viruses using serological data from 7924 European ancestry participants in the UK Biobank cohort.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. We identified specific amino acid (AA) residues that are associated with seroreactivity, the strongest associations presented in a range of AA positions within DR\u03b2i at positions 11, 13, 71, and 74 for Epstein-Barr Virus (EBV), Varicella Zoster Virus (VZV), Human Herpes virus 7, (HHV7) and Merkel cell polyomavirus (MCV). Genome-wide association analyses discovered 7 novel genetic loci outside the HLA associated with viral antibody response (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;5.0\u00d710\n                    <jats:sup>-8<\/jats:sup>\n                    ), including\n                    <jats:italic>FUT2<\/jats:italic>\n                    (19q13.33) for human polyomavirus BK (BKV),\n                    <jats:italic>STING1<\/jats:italic>\n                    (5q31.2) for MCV, as well as\n                    <jats:italic>CXCR5<\/jats:italic>\n                    (11q23.3) and\n                    <jats:italic>TBKBP1<\/jats:italic>\n                    (17q21.32) for HHV7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection, 12 outside of the HLA region, including\n                    <jats:italic>ECSCR<\/jats:italic>\n                    : P=5.0*10\n                    <jats:sup>-15<\/jats:sup>\n                    (MCV),\n                    <jats:italic>NTN5:<\/jats:italic>\n                    P=1.1\u00d710\n                    <jats:sup>-9<\/jats:sup>\n                    (BKV), and\n                    <jats:italic>P2RY13:<\/jats:italic>\n                    P=1.1\u00d710\n                    <jats:sup>-8<\/jats:sup>\n                    EBV nuclear antigen. We also demonstrated pleiotropy between viral response genes and complex diseases; from autoimmune disorders to cancer to neurodegenerative and psychiatric conditions.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants beyond the HLA that contribute to host-virus interaction.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.05.01.20088054","type":"posted-content","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T19:26:22Z","timestamp":1588879582000},"source":"Crossref","is-referenced-by-count":21,"title":["The landscape of host genetic factors involved in immune response to common viral infections"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3226-4727","authenticated-orcid":false,"given":"Linda","family":"Kachuri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen S.","family":"Francis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maike","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George A.","family":"Wendt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohan","family":"Boss\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3537-2608","authenticated-orcid":false,"given":"Taylor B.","family":"Cavazos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-6891","authenticated-orcid":false,"given":"Sara R.","family":"Rashkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elad","family":"Ziv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S.","family":"Witte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2021020610251356000_2020.05.01.20088054v3.1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13954"},{"key":"2021020610251356000_2020.05.01.20088054v3.2","doi-asserted-by":"crossref","unstructured":"Wang, W. et al. 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