{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T20:46:13Z","timestamp":1750797973010,"version":"3.37.3"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"name":"NICHD","award":["R01HD058008"],"award-info":[{"award-number":["R01HD058008"]}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"crossref","award":["Z01-ES103086"],"award-info":[{"award-number":["Z01-ES103086"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"crossref","award":["262700"],"award-info":[{"award-number":["262700"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n            Objective\u2003Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations.<\/jats:p><jats:p>\n            Study Design\u2003We conducted a nested case\u2013control study within the Norwegian Mother, Father and Child Birth Cohort (1999\u20132008) of 2,596 mother\u2013child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n\u2009=\u20091,915 with minor allele frequency \u226510%). We further investigated the influence of smoking cessation during pregnancy.<\/jats:p><jats:p>\n            Results\u2003Three polymorphisms showed overall (p\u2009&lt;\u20090.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p\u2009=\u20090.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p\u2009=\u20090.01).<\/jats:p><jats:p>\n            Conclusion\u2003Evidence for gene\u2013smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene\u2013environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures.<\/jats:p><jats:p>\n            Key Points\n          <\/jats:p>","DOI":"10.1055\/s-0041-1740072","type":"journal-article","created":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T23:31:51Z","timestamp":1638142311000},"page":"044-052","source":"Crossref","is-referenced-by-count":1,"title":["Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?"],"prefix":"10.1055","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-930X","authenticated-orcid":false,"given":"Anna E.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christy L.","family":"Avery","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"},{"name":"Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarice R.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew F.","family":"Olshan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quaker E.","family":"Harmon","sequence":"additional","affiliation":[{"name":"Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingchun","family":"Luo","sequence":"additional","affiliation":[{"name":"Mammalian Genotyping Core, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Manuck","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Wu","sequence":"additional","affiliation":[{"name":"Biostatistics and Biomathematics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari","family":"Klungs\u00f8yr","sequence":"additional","affiliation":[{"name":"Division for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway"},{"name":"Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lill","family":"Trogstad","sequence":"additional","affiliation":[{"name":"Division for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Magnus","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie M.","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North 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Tsai","year":"2008","journal-title":"Hum Genet"},{"issue":"06","key":"ref29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/10408440490519786","article-title":"Gene-environment interactions: a review of effects on reproduction and development","volume":"34","author":"A M Cummings","year":"2004","journal-title":"Crit Rev Toxicol"},{"issue":"08","key":"ref30","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/ng.3895","article-title":"FINNPEC Consortium. 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