In:
Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-9-21)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1664-8021
DOI:
10.3389/fgene.2021.721488
DOI:
10.3389/fgene.2021.721488.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606823-0
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