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

Rebecca Jean Schmidt, Robin L Hansen, Jaana Hartiala, Hooman Allayee, Jaime L. Sconberg, Linda C. Schmidt, Heather E. Volk, Flora Tassone

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)483-489
Number of pages7
JournalEarly Human Development
Volume91
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint

Vitamin D
Genes
Genotype
Alleles
Confidence Intervals
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Odds Ratio
Genomic Imprinting
Calcitriol Receptors
Autism Spectrum Disorder
Cognition
Population
Case-Control Studies
Logistic Models
Mothers
DNA
Research

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. / Schmidt, Rebecca Jean; Hansen, Robin L; Hartiala, Jaana; Allayee, Hooman; Sconberg, Jaime L.; Schmidt, Linda C.; Volk, Heather E.; Tassone, Flora.

In: Early Human Development, Vol. 91, No. 8, 01.08.2015, p. 483-489.

Research output: Contribution to journalArticle

Schmidt, Rebecca Jean ; Hansen, Robin L ; Hartiala, Jaana ; Allayee, Hooman ; Sconberg, Jaime L. ; Schmidt, Linda C. ; Volk, Heather E. ; Tassone, Flora. / Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. In: Early Human Development. 2015 ; Vol. 91, No. 8. pp. 483-489.
@article{f2d3b4b12b964a7f806aced2ff7cce2e,
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.",
keywords = "Autistic disorder, Genes, Interaction, Prevention, Trios, Vitamin D",
author = "Schmidt, {Rebecca Jean} and Hansen, {Robin L} and Jaana Hartiala and Hooman Allayee and Sconberg, {Jaime L.} and Schmidt, {Linda C.} and Volk, {Heather E.} and Flora Tassone",
year = "2015",
month = "8",
day = "1",
doi = "10.1016/j.earlhumdev.2015.05.008",
language = "English (US)",
volume = "91",
pages = "483--489",
journal = "Early Human Development",
issn = "0378-3782",
publisher = "Elsevier Ireland Ltd",
number = "8",

}

TY - JOUR

T1 - Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study

AU - Schmidt, Rebecca Jean

AU - Hansen, Robin L

AU - Hartiala, Jaana

AU - Allayee, Hooman

AU - Sconberg, Jaime L.

AU - Schmidt, Linda C.

AU - Volk, Heather E.

AU - Tassone, Flora

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

KW - Autistic disorder

KW - Genes

KW - Interaction

KW - Prevention

KW - Trios

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=84937437331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937437331&partnerID=8YFLogxK

U2 - 10.1016/j.earlhumdev.2015.05.008

DO - 10.1016/j.earlhumdev.2015.05.008

M3 - Article

C2 - 26073892

AN - SCOPUS:84937437331

VL - 91

SP - 483

EP - 489

JO - Early Human Development

JF - Early Human Development

SN - 0378-3782

IS - 8

ER -