{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:38:13Z","timestamp":1774928293472,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":308,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007192","name":"Rijksinstituut voor Volksgezondheid en Milieu","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007192","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Older persons generally have weaker antibody responses to vaccines than younger individuals, but heterogeneity is large. We aimed to identify genetic variants associated with primary SARS\u2010CoV\u20102 vaccine\u2010induced antibody responses in older persons that might contribute to this heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Demographic and genotype data were collected in the Doetinchem Cohort Study prior to the COVID\u201019 pandemic. Antibody responses were measured 1\u2009month after the first and second SARS\u2010CoV\u20102 vaccinations, and genome\u2010wide association analysis was performed in 842 and 890 individuals respectively. Polygenic scores were calculated and tested in an independent sample, and the variance explained by the scores was estimated using a bootstrap procedure. Genes were mapped to genome\u2010wide suggestive (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20091\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ) loci, and gene set enrichment was performed using the hypergeometric test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antibody responses 1\u2009month after the first and second SARS\u2010CoV\u20102 vaccinations were linked to genome\u2010wide significant (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) loci on Chromosome 5. Polygenic scores related to these antibody responses could explain 9% (95% CI P1: [\u22124% to 21%], 95% CI P2: [\u22124% to 24%]) of the variance. Genome\u2010wide suggestive loci related to the responses after two vaccinations could be mapped to several genes in the human leukocyte antigen (HLA) region on chromosome 6p21.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Genetic variation is suggested to play a role in the primary vaccine\u2010induced IgG antibody responses to SARS\u2010CoV\u20102 in older persons. The most prominent source of variation was found to lie in HLA genes, which are enriched in several immune pathways and immune\u2010mediated diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70058","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T17:42:20Z","timestamp":1762364540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic differences in the HLA region contribute to the variability in SARS\u2010CoV\u20102 vaccine responsiveness of older persons: the Doetinchem Cohort Study"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5075-3970","authenticated-orcid":false,"given":"Yunus","family":"Kuijpers","sequence":"first","affiliation":[{"name":"Centre for Prevention, Lifestyle and Health National Institute for Public Health and the Environment (RIVM)  Bilthoven The 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Monique","family":"Verschuren","sequence":"additional","affiliation":[{"name":"Centre for Prevention, Lifestyle and Health National Institute for Public Health and the Environment (RIVM)  Bilthoven The Netherlands"},{"name":"Julius Centre for Health Sciences and Primary Care University Medical Centre Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Marie","family":"Buisman","sequence":"additional","affiliation":[{"name":"Centre for Immunology of Infectious Diseases and Vaccines National Institute for Public Health and the Environment (RIVM)  Bilthoven The 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