title: Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study.
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.
authors.affiliation: 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.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Schmidt
authors.affiliation: 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.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Hansen
authors.affiliation: 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.
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.affiliation: 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.
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.affiliation: Graduate Group in Epidemiology, University of California Davis, Davis, CA, USA. Electronic address: jlsconberg@ucdavis.edu.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Sconberg
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA, USA. Electronic address: SchmidtLC@aol.com.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Schmidt
authors.affiliation: 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.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Volk
authors.affiliation: 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.
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D005220:Fathers; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human
keywords: Autistic disorder; Genes; Interaction; Prevention; Trios; Vitamin D