Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D
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 pregnan...
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Frontiers Media S.A.
2021-09-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.721488/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aparna Sampathkumar Karen M. Tan Li Chen Mary F. F. Chong Mary F. F. Chong Fabian Yap Fabian Yap Fabian Yap Keith M. Godfrey Keith M. Godfrey Yap Seng Chong Yap Seng Chong Peter D. Gluckman Peter D. Gluckman Adaikalavan Ramasamy Adaikalavan Ramasamy Neerja Karnani Neerja Karnani Neerja Karnani |
spellingShingle |
Aparna Sampathkumar Karen M. Tan Li Chen Mary F. F. Chong Mary F. F. Chong Fabian Yap Fabian Yap Fabian Yap Keith M. Godfrey Keith M. Godfrey Yap Seng Chong Yap Seng Chong Peter D. Gluckman Peter D. Gluckman Adaikalavan Ramasamy Adaikalavan Ramasamy Neerja Karnani Neerja Karnani Neerja Karnani Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D Frontiers in Genetics vitamin D ethnicity genome-wide association study pregnancy offspring GUSTO |
author_facet |
Aparna Sampathkumar Karen M. Tan Li Chen Mary F. F. Chong Mary F. F. Chong Fabian Yap Fabian Yap Fabian Yap Keith M. Godfrey Keith M. Godfrey Yap Seng Chong Yap Seng Chong Peter D. Gluckman Peter D. Gluckman Adaikalavan Ramasamy Adaikalavan Ramasamy Neerja Karnani Neerja Karnani Neerja Karnani |
author_sort |
Aparna Sampathkumar |
title |
Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D |
title_short |
Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D |
title_full |
Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D |
title_fullStr |
Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D |
title_full_unstemmed |
Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D |
title_sort |
genetic link determining the maternal-fetal circulation of vitamin d |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-09-01 |
description |
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=942), and the cord blood of their offspring at birth (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 (≤75nmol/L) during pregnancy. Antenatal 25OHD was associated with ethnicity [Malay (Β=−22.32nmol/L, p=2.3×10−26); Indian (Β=−21.85, p=3.1×10−21); reference Chinese], age (Β=0.47/year, p=0.0058), and supplement intake (Β=16.47, p=2.4×10−13). Cord blood 25OHD highly correlated with antenatal vitamin D (r=0.75) and was associated with ethnicity [Malay (Β=−4.44, p=2.2×10−7); Indian (Β=−1.99, p=0.038); reference Chinese]. GWAS analysis identified rs4588, a missense variant in the group-specific component (GC) gene encoding vitamin D binding protein (VDBP), and its defining haplotype, as a risk factor for low antenatal (Β=−8.56/T-allele, p=1.0×10−9) and cord blood vitamin D (Β=−3.22/T-allele, p=1.0×10−8) in all three ethnicities. We also discovered a novel association in a SNP downstream of CYP2J2 (rs10789082), a gene involved in 25-hydroxylation of vitamin D, with vitamin D in pregnant women (Β=−7.68/G-allele, p=1.5×10−8), but not their offspring. As the prevention and early detection of suboptimal vitamin D levels are of profound importance to both mother and offspring’s health, the genetic risk variants identified in this study allow risk assessment and precision in early intervention of vitamin D deficiency. |
topic |
vitamin D ethnicity genome-wide association study pregnancy offspring GUSTO |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2021.721488/full |
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doaj-900ead58e96d45a99d3b1f663cdbce7d2021-09-21T06:10:17ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-09-011210.3389/fgene.2021.721488721488Genetic Link Determining the Maternal-Fetal Circulation of Vitamin DAparna Sampathkumar0Karen M. Tan1Li Chen2Mary F. F. Chong3Mary F. F. Chong4Fabian Yap5Fabian Yap6Fabian Yap7Keith M. Godfrey8Keith M. Godfrey9Yap Seng Chong10Yap Seng Chong11Peter D. Gluckman12Peter D. Gluckman13Adaikalavan Ramasamy14Adaikalavan Ramasamy15Neerja Karnani16Neerja Karnani17Neerja Karnani18Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSaw Swee Hock School of Public Health (SSHPH), National University of Singapore (NUS), Singapore, SingaporeDepartment of Pediatric Endocrinology, KK Women’s and Children’s Hospital, Singapore, SingaporeDuke-NUS Medical School, Singapore, SingaporeMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United KingdomLee Kong Chian School of Medicine, Singapore, SingaporeDepartment of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital, Southampton, United KingdomSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeLiggins Institute, University of Auckland, Auckland, New ZealandSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore0Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore1Department of Biochemistry, National University of Singapore (NUS), Singapore, Singapore2Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeVitamin 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=942), and the cord blood of their offspring at birth (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 (≤75nmol/L) during pregnancy. Antenatal 25OHD was associated with ethnicity [Malay (Β=−22.32nmol/L, p=2.3×10−26); Indian (Β=−21.85, p=3.1×10−21); reference Chinese], age (Β=0.47/year, p=0.0058), and supplement intake (Β=16.47, p=2.4×10−13). Cord blood 25OHD highly correlated with antenatal vitamin D (r=0.75) and was associated with ethnicity [Malay (Β=−4.44, p=2.2×10−7); Indian (Β=−1.99, p=0.038); reference Chinese]. GWAS analysis identified rs4588, a missense variant in the group-specific component (GC) gene encoding vitamin D binding protein (VDBP), and its defining haplotype, as a risk factor for low antenatal (Β=−8.56/T-allele, p=1.0×10−9) and cord blood vitamin D (Β=−3.22/T-allele, p=1.0×10−8) in all three ethnicities. We also discovered a novel association in a SNP downstream of CYP2J2 (rs10789082), a gene involved in 25-hydroxylation of vitamin D, with vitamin D in pregnant women (Β=−7.68/G-allele, p=1.5×10−8), but not their offspring. As the prevention and early detection of suboptimal vitamin D levels are of profound importance to both mother and offspring’s health, the genetic risk variants identified in this study allow risk assessment and precision in early intervention of vitamin D deficiency.https://www.frontiersin.org/articles/10.3389/fgene.2021.721488/fullvitamin Dethnicitygenome-wide association studypregnancyoffspringGUSTO |