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Relative risks and 95% confidence intervals were estimated using log-linear free response models, adjusting for correlation between familial genotypes. Relative risk of severe-spectrum hypertensive disorder of pregnancy was increased with double-dose carriage of the T allele for SNP rs4902080 in both mother [RR 6.96, <jats:italic>p<\/jats:italic>\u2009=\u20090.028] and child [RR 5.77, <jats:italic>p<\/jats:italic>\u2009=\u20090.031]. Child double-dose of the T allele for SNP rs10144958 [RR 5.52, <jats:italic>p<\/jats:italic>\u2009=\u20090.047] also increased risk. The heterozygous genotype (CT) for SNPs rs2057482 and rs11549465 was protective against hypertensive disorders of pregnancy when carried by mother [rs2057482: RR 0.34, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; rs11549465: RR 0.23, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001] or child [rs2057482: RR 0.44, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; rs11549465: RR 0.31, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001]. A single copy of the C-c-c-G haplotype (rs4902080-rs2057482-rs11549465-rs10144958, <jats:italic>N<\/jats:italic>\u2009=\u2009147), conferred decreased risk versus the C-T-T-G haplotype in mother [RR 0.28, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001] and child [RR 0.36, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001]. No parent-of-origin effects were seen. We conclude that polymorphism changes and haplotypes in the HIF-1\u03b1 gene of mothers, fathers, and children are associated with risk for severe-spectrum hypertensive disorders of pregnancy.<\/jats:p>","DOI":"10.1007\/s43032-025-01835-5","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T14:09:43Z","timestamp":1741961383000},"page":"993-1002","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypoxia-Inducible Factor 1-Alpha Gene Polymorphisms Impact Risk of Severespectrum Hypertensive Disorders of Pregnancy: A Case-Control Study"],"prefix":"10.1007","volume":"32","author":[{"given":"Claire","family":"Baldauf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor A.","family":"Pickering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Grubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kon","family":"Gjessing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7785-4221","authenticated-orcid":false,"given":"Melissa L.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"1835_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.preghy.2018.05.004","volume":"13","author":"MA Brown","year":"2018","unstructured":"Brown MA, Magee LA, Kenny LC, et al. 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