Association and gene-gene interaction of SLC6A4 and ITGB3 in autism.
Am J Med Genet B Neuropsychiatr Genet
; 153B(2): 477-483, 2010 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-19588468
ABSTRACT
Autism is a heritable neurodevelopmental disorder with substantial genetic heterogeneity. Studies point to possible links between autism and two serotonin related genes SLC6A4 and ITGB3 with a sex-specific genetic effect and interaction between the genes. Despite positive findings, inconsistent results have complicated interpretation. This study seeks to validate and clarify previous findings in an independent dataset taking into account sex, family-history (FH) and gene-gene effects. Family-based association analysis was performed within each gene. Gene-gene interactions were tested using extended multifactor dimensionality reduction (EMDR) and MDR-phenomics (MDR-P) using sex of affecteds and FH as covariates. No significant associations with individual SNPs were found in the datasets stratified by sex, but associations did emerge when we stratified by family history. While not significant in the overall dataset, nominally significant association was identified at RS2066713 (P = 0.006) within SLC6A4 in family-history negative (FH-) families, at RS2066713 (P = 0.038) in family-history positive (FH+) families but with the opposite risk allele as in the FH- families. For ITGB3, nominally significant association was identified at RS3809865 overall (P = 0.040) and within FH+ families (P = 0.031). However, none of the associations survived the multiple testing correction. MDR-P confirmed gene-gene effects using sex of affecteds (P = 0.023) and family history (P = 0.014, survived the multiple testing corrections) as covariates. Our results indicate the extensive heterogeneity within these two genes among families. The potential interaction between SLC6A4 and ITGB3 may be clarified using family history as an indicator of genetic architecture, illustrating the importance of covariates as markers of heterogeneity in genetic analyses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
/
Integrina beta3
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Proteínas da Membrana Plasmática de Transporte de Serotonina
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Modelos Genéticos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Med Genet B Neuropsychiatr Genet
Assunto da revista:
GENETICA MEDICA
/
NEUROLOGIA
/
PSIQUIATRIA
Ano de publicação:
2010
Tipo de documento:
Article