{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:02Z","timestamp":1787026502676,"version":"build-2736575974"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001355","name":"Singapore Institute for Clinical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001355","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Vitamin D is an essential micronutrient whose demand is heightened during pregnancy to support the growth of the fetus. Furthermore, the fetus does not produce vitamin D and hence relies exclusively on the supply of maternal vitamin D through the placenta. Vitamin D inadequacy is linked with pregnancy complications and adverse infant outcomes. Hence, early predictive markers of vitamin D inadequacy such as genetic vulnerability are important to both mother and offspring. In this multi-ethnic Asian birth cohort study, we report the first genome-wide association analysis (GWAS) of maternal and fetal vitamin D in circulation. For this, 25-hydroxyvitamin D (25OHD) was measured in the antenatal blood of mothers during mid gestation (\n                    <jats:italic>n<\/jats:italic>\n                    =942), and the cord blood of their offspring at birth (\n                    <jats:italic>n<\/jats:italic>\n                    =812). Around ~7 million single nucleotide polymorphisms (SNPs) were regressed against 25OHD concentrations to identify genetic risk variants. About 41% of mothers had inadequate 25OHD (\u226475nmol\/L) during pregnancy. Antenatal 25OHD was associated with ethnicity [Malay (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u221222.32nmol\/L,\n                    <jats:italic>p<\/jats:italic>\n                    =2.3\u00d710\n                    <jats:sup>\u221226<\/jats:sup>\n                    ); Indian (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u221221.85,\n                    <jats:italic>p<\/jats:italic>\n                    =3.1\u00d710\n                    <jats:sup>\u221221<\/jats:sup>\n                    ); reference Chinese], age (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =0.47\/year,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0058), and supplement intake (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =16.47,\n                    <jats:italic>p<\/jats:italic>\n                    =2.4\u00d710\n                    <jats:sup>\u221213<\/jats:sup>\n                    ). Cord blood 25OHD highly correlated with antenatal vitamin D (\n                    <jats:italic>r<\/jats:italic>\n                    =0.75) and was associated with ethnicity [Malay (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u22124.44,\n                    <jats:italic>p<\/jats:italic>\n                    =2.2\u00d710\n                    <jats:sup>\u22127<\/jats:sup>\n                    ); Indian (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u22121.99,\n                    <jats:italic>p<\/jats:italic>\n                    =0.038); reference Chinese]. GWAS analysis identified rs4588, a missense variant in the group-specific component (\n                    <jats:italic>GC<\/jats:italic>\n                    ) gene encoding vitamin D binding protein (VDBP), and its defining haplotype, as a risk factor for low antenatal (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u22128.56\/T-allele,\n                    <jats:italic>p<\/jats:italic>\n                    =1.0\u00d710\n                    <jats:sup>\u22129<\/jats:sup>\n                    ) and cord blood vitamin D (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u22123.22\/T-allele,\n                    <jats:italic>p<\/jats:italic>\n                    =1.0\u00d710\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) in all three ethnicities. We also discovered a novel association in a SNP downstream of\n                    <jats:italic>CYP2J2<\/jats:italic>\n                    (rs10789082), a gene involved in 25-hydroxylation of vitamin D, with vitamin D in pregnant women (\n                    <jats:italic>\u0392<\/jats:italic>\n                    =\u22127.68\/G-allele,\n                    <jats:italic>p<\/jats:italic>\n                    =1.5\u00d710\n                    <jats:sup>\u22128<\/jats:sup>\n                    ), but not their offspring. As the prevention and early detection of suboptimal vitamin D levels are of profound importance to both mother and offspring\u2019s health, the genetic risk variants identified in this study allow risk assessment and precision in early intervention of vitamin D deficiency.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2021.721488","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T02:13:00Z","timestamp":1632190380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D"],"prefix":"10.3389","volume":"12","author":[{"given":"Aparna","family":"Sampathkumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F. F.","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith M.","family":"Godfrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yap Seng","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Gluckman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adaikalavan","family":"Ramasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neerja","family":"Karnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3390\/nu10040478","article-title":"Vitamin D deficiency and antenatal and postpartum depression: a systematic review","volume":"10","author":"Aghajafari","year":"2018","journal-title":"Nutrients"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"f1169","DOI":"10.1136\/bmj.f1169","article-title":"Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies","volume":"346","author":"Aghajafari","year":"2013","journal-title":"BMJ"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1093\/hmg\/ddq155","article-title":"Genome-wide association study of circulating vitamin D levels","volume":"19","author":"Ahn","year":"2010","journal-title":"Hum. 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Nutr."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.721488\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T02:13:07Z","timestamp":1632190387000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.721488\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,21]]},"references-count":55,"alternative-id":["10.3389\/fgene.2021.721488"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.721488","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,21]]},"article-number":"721488"}}