1. Genetic Contributions to Maternal and Neonatal Vitamin D Levels
- Author
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Traglia, Michela, Windham, Gayle C, Pearl, Michelle, Poon, Victor, Eyles, Darryl, Jones, Karen L, Lyall, Kristen, Kharrazi, Martin, Croen, Lisa A, and Weiss, Lauren A
- Subjects
Genetics ,Infant Mortality ,Brain Disorders ,Mental Health ,Pediatric ,Perinatal Period - Conditions Originating in Perinatal Period ,Prevention ,Preterm ,Low Birth Weight and Health of the Newborn ,Intellectual and Developmental Disabilities (IDD) ,Nutrition ,Autism ,Aetiology ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Underpinning research ,Reproductive health and childbirth ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Autism Spectrum Disorder ,Chemokine CXCL6 ,Duffy Blood-Group System ,Female ,Fetal Blood ,Humans ,Infant ,Newborn ,Interleukin-8 ,Polymorphism ,Single Nucleotide ,Pregnancy ,Protein Kinase C ,Receptors ,Cell Surface ,Vitamin D ,Vitamin D-Binding Protein ,vitamin D ,GC pregnancy ,neonates ,immune function ,maternal and fetal genetics ,GWAS ,SNP-based heritability ,early development ,autism ,intellectual disability ,Developmental Biology - 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. more...
- Published
- 2020