Objectives: To replicate our preliminary findings with a second dataset.
Methods: We used the Weinberg log-linear method to analyze existing GWAS data from 1366 families in the Autism Genome Project (AGP) genotyped on the Illumina 1M array.
Results: The AGP dataset showed genome-wide significance (p = 1.83E-19) for SNP rs12636481, located near rs12487874 and not in the earlier dataset. SNP rs12487874 was not part of the AGP dataset. Both SNPs showed a marked asymmetry in parents in both studies, where the mothers identified were homozygotes for the minor allele.
Conclusions: Since this study confirmed a peak for autism in a small region of chromosome 3p24.3, we plan to analyze data from a much larger dataset, the Simons Simplex Collection (SSC), to confirm and extend these findings. We will also re-genotype the SNPs identified using a more stringent method to confirm these findings and to exclude possible artifacts. If these findings are confirmed by analysis in the SSC and re-genotyping, we will then test the hypothesis that a structural DNA variant in this region is responsible for the observed effect. These studies could lead to identification of DNA variation in this region whose action may contribute to autism. We hope these studies will lead to better understanding of the pathogenesis of autism, to approaches to identifying risk of autism prenatally or even before the onset of pregnancy, and perhaps to methods of preventing or treating autism at a very early stage.
See more of: Genetic Factors in ASD
See more of: Biological Mechanisms