{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:55:46Z","timestamp":1790567746891,"version":"4.1.0"},"reference-count":93,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL163234"],"award-info":[{"award-number":["R01 HL163234"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL146963"],"award-info":[{"award-number":["K08 HL146963"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R03 HL162756"],"award-info":[{"award-number":["R03 HL162756"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004060","name":"Preeclampsia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal\u2013fetal interface central to its pathogenesis. The highly polymorphic HLA region mediates maternal immune tolerance of the semi\u2010allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi\u2010ancestry TOPMed Boston\u2013Colombia Collaborative for Adverse Pregnancy Outcomes (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912,790; 4770 PE, 8020 controls; 10,808 maternal, 1982 fetal, including 1848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub\u2010phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (&gt;\u200980%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across Class I loci showed a protective effect in preterm PE (OR\u2009=\u20090.81, 95% CI: 0.68\u20130.97), with a similar pattern for HLA\u2010A heterozygosity (OR\u2009=\u20090.78, 95% CI: 0.64\u20130.97). In contrast, fetal heterozygosity at HLA\u2010DQB1 was nominally associated with increased risk of PE (OR\u2009=\u20091.36, 95% CI: 1.03\u20131.80) and preterm PE (OR\u2009=\u20091.73, 95% CI: 1.13\u20132.74). No individual maternal or fetal HLA alleles were associated with PE. Maternal\u2013fetal mismatch analysis demonstrated locus\u2010specific associations with preterm PE, including increased risk with HLA\u2010DQA1 mismatch and reduced risk with HLA\u2010C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity\u2014rather than individual alleles alone\u2014in studies of PE aetiology.\n                  <\/jats:p>","DOI":"10.1111\/tan.70970","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:01:21Z","timestamp":1789178481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal and Fetal\n                    <scp>HLA<\/scp>\n                    Heterozygosity in Preeclampsia: Insights From a Large Multi\u2010Ancestry Pregnancy Cohort"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-8807","authenticated-orcid":false,"given":"Chang","family":"Cao","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Medical and Population Genetics The Broad Institute of MIT and Harvard  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Maher","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Medical and Population Genetics The Broad Institute of MIT and Harvard  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8282-4895","authenticated-orcid":false,"given":"Jie","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Medical and Population Genetics The Broad Institute of MIT and Harvard  Boston Massachusetts USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. 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