{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T01:48:46Z","timestamp":1785808126406,"version":"3.56.0"},"reference-count":152,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Manitoba Liquor and Lotteries","award":["55380"],"award-info":[{"award-number":["55380"]}]},{"name":"Manitoba Liquor and Lotteries","award":["313152"],"award-info":[{"award-number":["313152"]}]},{"name":"Manitoba Liquor and Lotteries","award":["51270"],"award-info":[{"award-number":["51270"]}]},{"name":"Manitoba Liquor and Lotteries","award":["54525"],"award-info":[{"award-number":["54525"]}]},{"name":"Manitoba Medical Service Foundation","award":["55380"],"award-info":[{"award-number":["55380"]}]},{"name":"Manitoba Medical Service Foundation","award":["313152"],"award-info":[{"award-number":["313152"]}]},{"name":"Manitoba Medical Service Foundation","award":["51270"],"award-info":[{"award-number":["51270"]}]},{"name":"Manitoba Medical Service Foundation","award":["54525"],"award-info":[{"award-number":["54525"]}]},{"name":"Canadian Institutes of Health Research","award":["55380"],"award-info":[{"award-number":["55380"]}]},{"name":"Canadian Institutes of Health Research","award":["313152"],"award-info":[{"award-number":["313152"]}]},{"name":"Canadian Institutes of Health Research","award":["51270"],"award-info":[{"award-number":["51270"]}]},{"name":"Canadian Institutes of Health Research","award":["54525"],"award-info":[{"award-number":["54525"]}]},{"name":"Research Manitoba\/Children\u2019s Hospital Research Institute of Manitoba MSc Studentship and Kid\u2019s Brain Health Network","award":["55380"],"award-info":[{"award-number":["55380"]}]},{"name":"Research Manitoba\/Children\u2019s Hospital Research Institute of Manitoba MSc Studentship and Kid\u2019s Brain Health Network","award":["313152"],"award-info":[{"award-number":["313152"]}]},{"name":"Research Manitoba\/Children\u2019s Hospital Research Institute of Manitoba MSc Studentship and Kid\u2019s Brain Health Network","award":["51270"],"award-info":[{"award-number":["51270"]}]},{"name":"Research Manitoba\/Children\u2019s Hospital Research Institute of Manitoba MSc Studentship and Kid\u2019s Brain Health Network","award":["54525"],"award-info":[{"award-number":["54525"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder that affects an estimated 2\u20135% of North Americans. FASD is induced by prenatal alcohol exposure (PAE) during pregnancy and while there is a clear genetic contribution, few genetic factors are currently identified or understood. In this study, using a candidate gene approach, we performed a genetic variant analysis of retinoic acid (RA) metabolic and developmental signaling pathway genes on whole exome sequencing data of 23 FASD-diagnosed individuals. We found risk and resilience alleles in ADH and ALDH genes known to normally be involved in alcohol detoxification at the expense of RA production, causing RA deficiency, following PAE. Risk and resilience variants were also identified in RA-regulated developmental pathway genes, especially in SHH and WNT pathways. Notably, we also identified significant variants in the causative genes of rare neurodevelopmental disorders sharing comorbidities with FASD, including STRA6 (Matthew\u2013Wood), SOX9 (Campomelic Dysplasia), FDG1 (Aarskog), and 22q11.2 deletion syndrome (TBX1). Although this is a small exploratory study, the findings support PAE-induced RA deficiency as a major etiology underlying FASD and suggest risk and resilience variants may be suitable biomarkers to determine the risk of FASD outcomes following PAE.<\/jats:p>","DOI":"10.3390\/biom14050569","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes"],"prefix":"10.3390","volume":"14","author":[{"given":"Leo","family":"McKay","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berardino","family":"Petrelli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Pind","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-1095","authenticated-orcid":false,"given":"Richard F.","family":"Wintle","sequence":"additional","affiliation":[{"name":"The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert E.","family":"Chudley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3A 1S1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Dr\u00f6gem\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Centre on Aging, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6368-0416","authenticated-orcid":false,"given":"Abraham","family":"Fainsod","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12271, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Scherer","sequence":"additional","affiliation":[{"name":"The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada"},{"name":"Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, ON M5G 1L7, Canada"},{"name":"Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Hanlon-Dearman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3A 1S1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4688-2312","authenticated-orcid":false,"given":"Geoffrey G.","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Children\u2019s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Popova, S., Lange, S., Poznyak, V., Chudley, A.E., Shield, K.D., Reynolds, J.N., Murray, M., and Rehm, J. 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