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This study evaluates nongenetic factors associated with holoprosencephaly risk, severity, and gene\u2013environment interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For this retrospective case control study, we developed an online questionnaire focusing on exposures to common and rare toxins\/toxicants before and during pregnancy, nutritional factors, maternal health history, and demographic factors. Patients with holoprosencephaly were primarily ascertained from our ongoing genetic and clinical studies of holoprosencephaly. Controls included children with Williams\u2010Beuren syndrome (WBS) ascertained through online advertisements in a WBD support group and fliers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Difference in odds of exposures between cases and controls as well as within cases with varying holoprosencephaly severity were studied. Cases included children born with holoprosencephaly (\n                      <jats:italic>n<\/jats:italic>\n                      =\u200992) and the control group consisted of children with WBS (\n                      <jats:italic>n<\/jats:italic>\n                      =\u200956). Pregnancy associated risk associated with holoprosencephaly included maternal pregestational diabetes (9.2% of cases and 0 controls,\n                      <jats:italic>p<\/jats:italic>\n                      =\u2009.02), higher alcohol consumption (adjusted odds ratio [aOR], 1.73; 95% CI, 0.88\u201315.71), and exposure to consumer products such as aerosols or sprays including hair sprays (aOR, 2.46; 95% CI, 0.89\u20137.19). Significant gene\u2013environment interactions were identified including for consumption of cheese (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u2009.05) and espresso drinks (\n                      <jats:italic>p<\/jats:italic>\n                      =\u2009.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study identifies modifiable risk factors and gene\u2013environment interactions that should be considered in future prevention of holoprosencephaly. Studies with larger HPE cohorts will be needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.1834","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T04:34:50Z","timestamp":1603859690000},"page":"63-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Identifying environmental risk factors and\n                    <scp>gene\u2013environment<\/scp>\n                    interactions in holoprosencephaly"],"prefix":"10.1002","volume":"113","author":[{"given":"Yonit A.","family":"Addissie","sequence":"first","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute, The National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Troia","sequence":"additional","affiliation":[{"name":"Cardiovascular &amp; Pulmonary Branch National Heart, Lung, and Blood Institute, The National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Cardiovascular &amp; Pulmonary Branch National Heart, Lung, and Blood Institute, The National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Everson","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Molecular and Environmental Toxicology Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Kozel","sequence":"additional","affiliation":[{"name":"Cardiovascular &amp; Pulmonary Branch National Heart, Lung, and Blood Institute, The National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Muenke","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute, The National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Lipinski","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, School of Veterinary Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Molecular and Environmental Toxicology Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.C.","family":"Malecki","sequence":"additional","affiliation":[{"name":"Molecular and Environmental Toxicology Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Population Health Sciences, School of Medicine and Public Health University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-0875","authenticated-orcid":false,"given":"Paul","family":"Kruszka","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute, The National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12940-020-00611-z","article-title":"Prenatal exposure to pesticides and risk for holoprosencephaly: A case\u2010control study","volume":"19","author":"Addissie Y. 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