Dataset Information

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.

ABSTRACT: The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.46-0.95) and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37-0.89). Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46-0.94). These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males.

SUBMITTER: Park HJ

PROVIDER: S-EPMC5000625 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.

Park Hae Jeong HJ Kim Su Kang SK Kang Won Sub WS Park Jin Kyung JK Kim Young Jong YJ Nam Min M Kim Jong Woo JW Chung Joo-Ho JH

International journal of molecular sciences 20160729 8

The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were gen ...[more]

PMID: 27483248

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Project description:BackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 × 10- 7. Seven CpGs showed differences at p < 1 × 10- 5 and 48 at 1 × 10- 4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds.ConclusionsNo single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.

Dataset Information

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.

Publications

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.

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