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Early Hum Dev. 2015 Aug;91(8):483-9. doi: 10.1016/j.earlhumdev.2015.05.008. Epub 2015 Jun 11.

Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study.

Author information

1
Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA, USA; Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis, Sacramento, CA, USA. Electronic address: rjschmidt@ucdavis.edu.
2
Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis, Sacramento, CA, USA; Department of Pediatrics, University of California Davis School of Medicine, Davis, CA, USA. Electronic address: rlhansen@ucdavis.edu.
3
Department of Preventive Medicine, Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. Electronic address: hartiala@usc.edu.
4
Department of Preventive Medicine, Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. Electronic address: hallayee@usc.edu.
5
Graduate Group in Epidemiology, University of California Davis, Davis, CA, USA. Electronic address: jlsconberg@ucdavis.edu.
6
Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA, USA. Electronic address: SchmidtLC@aol.com.
7
Departments of Preventive Medicine and Pediatrics, Zilkha Neurogenetic Institute, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA. Electronic address: hvolk@usc.edu.
8
Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis, Sacramento, CA, USA; Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA, USA. Electronic address: ftassone@ucdavis.edu.

Abstract

BACKGROUND:

Vitamin D is essential for proper neurodevelopment and cognitive and behavioral function. We examined associations between autism spectrum disorder (ASD) 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 (n=474) or typical development (TD, n=281). Maternal, paternal, and child DNA samples for 384 (81%) families of children with ASD and 234 (83%) families of TD children were genotyped for: TaqI, BsmI, FokI, and Cdx2 in the vitamin D receptor (VDR) 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 (CI) for each allelic variant.

RESULTS:

Paternal VDR TaqI homozygous variant genotype was significantly associated with ASD in case-control analysis (odds ratio [OR] [CI]: 6.3 [1.9-20.7]) and there was a trend towards increased risk associated with VDR BsmI (OR [CI]: 4.7 [1.6-13.4]). 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.

KEYWORDS:

Autistic disorder; Genes; Interaction; Prevention; Trios; Vitamin D

PMID:
26073892
PMCID:
PMC4871694
DOI:
10.1016/j.earlhumdev.2015.05.008
[Indexed for MEDLINE]
Free PMC Article

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