Genetic Contributions to Maternal and Neonatal Vitamin D Levels

Genetics. 2020 Apr;214(4):1091-1102. doi: 10.1534/genetics.119.302792. Epub 2020 Feb 11.


Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal midgestational serum-derived and neonatal blood-spot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the GC gene, encoding the binding protein for the transport and function of vitamin D. We also found suggestive cross-associated loci for neonatal and maternal vitamin D near immune genes, such as CXCL6-IL8 and ACKR1 We found no interactions with ASD. However, when including a set of cases with intellectual disability but not ASD (N = 179), we observed a suggestive interaction between decreased levels of neonatal vitamin D and a specific maternal genotype near the PKN2 gene. Our results suggest that genetic variation influences total vitamin D levels during pregnancy and at birth via proteins in the vitamin D pathway, but also potentially via distinct mechanisms involving loci with known roles in immune function that might be involved in vitamin D pathophysiology in pregnancy.

Keywords: GC pregnancy; GWAS; SNP-based heritability; autism; early development; immune function; intellectual disability; maternal and fetal genetics; neonates; vitamin D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autism Spectrum Disorder / genetics*
  • Chemokine CXCL6 / genetics
  • Duffy Blood-Group System / genetics
  • Female
  • Fetal Blood / metabolism*
  • Humans
  • Infant, Newborn
  • Interleukin-8 / genetics
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Protein Kinase C / genetics
  • Receptors, Cell Surface / genetics
  • Vitamin D / blood
  • Vitamin D / genetics*
  • Vitamin D-Binding Protein / genetics


  • ACKR1 protein, human
  • CXCL6 protein, human
  • Chemokine CXCL6
  • Duffy Blood-Group System
  • GC protein, human
  • Interleukin-8
  • Receptors, Cell Surface
  • Vitamin D-Binding Protein
  • Vitamin D
  • protein kinase N
  • Protein Kinase C