International Meeting for Autism Research: Selected Vitamin D Metabolic Gene Variants and Risk for Autism Spectrum Disorders In the CHARGE Study

Selected Vitamin D Metabolic Gene Variants and Risk for Autism Spectrum Disorders In the CHARGE Study

Thursday, May 12, 2011
Elizabeth Ballroom E-F and Lirenta Foyer Level 2 (Manchester Grand Hyatt)
1:00 PM
R. J. Schmidt1, R. L. Hansen2,3, J. Hartiala4, H. Allayee4, L. C. Schmidt5, F. Tassone5 and I. Hertz-Picciotto1, (1)Department of Public Health Sciences, University of California Davis, Davis, CA, (2)University of California, Davis, MIND Institute, Sacramento, CA, (3)MIND Institute and Dept. of Pediatrics, University of California Davis, Davis, CA, (4)Department of Preventive Medicine, Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, (5)Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA

Causes of autism are unknown, though genetic contributions are well-accepted. Sufficient levels of vitamin D are essential for proper neurodevelopment, cognitive and behavioral function, and suppression of autoimmune and inflammatory responses. Associations between autism and gene variants in the vitamin D pathway have not been reported.


To examine associations between autism and common, functional polymorphisms involved in vitamin D uptake and metabolism in maternal, paternal, and child blood samples.


Northern California families were enrolled from 2003-2009 in the population-based case-control CHARGE (Childhood Autism Risks from Genetics and the Environment) Study.  Children aged 24-60 months were evaluated and confirmed to have autism spectrum disorder (ASD, n=474), or typical development (TD, n=281) at the University of California, Davis M.I.N.D. Institute using standardized clinical assessments, including: the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview–Revised, Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and the Social Communication Questionnaire. Adjusted odds ratios (OR) were estimated for associations between autism and maternal, paternal, and child TaqI, BsmI, FokI, Cdx2, variants in the vitamin D receptor (VDR) gene, and CYP27B1 rs4646536, VBP rs4588, and CYP2R1 rs10741657 genotypes.


DNA samples were provided and genotyped for 384 (81%) families of children with ASD and 234 (83%) families of TD children. Paternal homozygous variant genotypes for the TaqI and BsmI polymorphisms on the VDR gene, and CYP27B1 rs4646536 were associated with significantly increased risk for ASD when compared to the combination of homozygous wild type and heterozygous genotypes (OR=6.3, 95% confidence interval [CI]: 1.9-20.7; OR=4.7, 95% CI: 1.6-13.4; and OR=2.2, 95% CI: 1.0-4.9, respectively). Results were similar when the case group was limited to children meeting criteria for autism (n=264). There was no confounding by race, or other demographic variables. Only VBP rs4588 showed evidence for vulnerability to population structure bias.


This study provides preliminary evidence that paternal vitamin D metabolism might play a role in the etiology of ASD, but there were limitations due to the sample size.

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