Genetic Contributions to Maternal and Neonatal Vitamin D Levels.

Abstract

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.

• Authors: Michela Traglia, Gayle C Windham, Michelle Pearl, Victor Poon, Darryl Eyles, Karen L Jones, Kristen Lyall, Martin Kharrazi, Lisa A Croen, Lauren A Weiss
• Journal: Genetics (Genetics) Vol. 214 Issue 4 Pg. 1091-1102 (04 2020) ISSN: 1943-2631 [Electronic] United States
• PMID: 32047095 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 by the Genetics Society of America.

Chemical References

• 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

Topics

• 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, genetics)
• Vitamin D-Binding Protein (genetics)