{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:18:40Z","timestamp":1768562320460,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,1]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":53,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec id=\"s1a\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We have previously described genetic polymorphisms in candidate genes that are associated with inter-individual variations in antibody responses to mumps vaccination. To expand upon our previous work, we performed a genome-wide association study (GWAS) to discover host genetic variants associated with mumps vaccine-induced cellular immune responses.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s1b\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a GWAS of mumps-specific immune response outcomes (11 secreted cytokines\/chemokines) in a cohort of 1,406 subjects.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s1c\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Among the 11 cytokine\/chemokines we studied, four (IFN-\u03b3, IL-2, IL-1\u03b2, and TNF\u03b1) demonstrated GWAS signals reaching genome-wide significance (p&lt;5 x 10\n                    <jats:sup>-8<\/jats:sup>\n                    ). A genomic region (encoding Sialic acid-binding immunoglobulin-type lectins\/SIGLEC) located on chromosome 19q13 (p&lt;5\u00d710\n                    <jats:sup>-8<\/jats:sup>\n                    ) was associated with both IL-1\u03b2 and TNF\u03b1 responses. The SIGLEC5\/SIGLEC14 region contained 11 statistically significant single nucleotide polymorphisms (SNPs), including the intronic SIGLEC5 rs872629 (p=1.3E-11) and rs1106476 (p=1.32E-11) whose alternate alleles were significantly associated with decreased levels of mumps-specific IL-1\u03b2 (rs872629, p=1.77E-09; rs1106476, p=1.78E-09) and TNF\u03b1 (rs872629, p=1.3E-11; rs1106476, p=1.32E-11) production.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s1d\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results suggest that SNPs in the SIGLEC5\/SIGLEC14 genes play a role in cellular and inflammatory immune responses to mumps vaccination. These findings motivate further research into the functional roles of SIGLEC genes in the regulation of mumps vaccine-induced immunity.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.04.27.23289213","type":"posted-content","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T01:15:19Z","timestamp":1682990119000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-Wide Determinants of Cellular Immune Responses to Mumps Vaccine"],"prefix":"10.64898","author":[{"given":"Inna G.","family":"Ovsyannikova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iana H.","family":"Haralambieva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Schaid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathaniel D.","family":"Warner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory A.","family":"Poland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard B.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023050410400707000_2023.04.27.23289213v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706589"},{"key":"2023050410400707000_2023.04.27.23289213v1.2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06125-11"},{"key":"2023050410400707000_2023.04.27.23289213v1.3","doi-asserted-by":"crossref","unstructured":"Grose, C ., From King Nebuchadnezzar of Babylon to Mumps Genotyping and Vaccination 26 Centuries Later. 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