Abstract

© 2015. Background: Vitamin D is essential for proper neurodevelopment and cognitive and behavioral function. We examined associations between autism spectrum disorder and common, functional polymorphisms in vitamin D pathways. Methods: Children aged 24-60 months enrolled from 2003 to 2009 in the population-based CHARGE case-control study were evaluated clinically and confirmed to have ASD or typical development. Maternal, paternal, and child DNA samples for 384 families of children with ASD and 234 families of TD children were genotyped for: TaqI, BsmI, FokI, and Cdx2 in the vitamin D receptor gene, and CYP27B1 rs4646536, GC rs4588, and CYP2R1 rs10741657. Case-control logistic regression, family-based log-linear, and hybrid log-linear analyses were conducted to produce risk estimates and 95% confidence intervals for each allelic variant. Results: Paternal VDR TaqI homozygous variant genotype was significantly associated with ASD in case-control analysis and there was a trend towards increased risk associated with VDR BsmI. Log-linear triad analyses detected parental imprinting, with greater effects of paternally-derived VDR alleles. Child GC AA-genotype/A-allele was associated with ASD in log-linear and ETDT analyses. A significant association between decreased ASD risk and child CYP2R1 AA-genotype was found in hybrid log-linear analysis. There were limitations of low statistical power for less common alleles due to missing paternal genotypes. Conclusions: This study provides preliminary evidence that paternal and child vitamin D metabolism could play a role in the etiology of ASD; further research in larger study populations is warranted.