Components of environmental and genetic vulnerability suggest subgroups of severe autism spectrum disorder patients

The aim of this study is to investigate differences in genomic features and biological pathways according to a genetic environment continuum in autism vulnerability in ASD samples phenotypically homogeneous . First, we searched components of vulnerability based on risk factors: mother schooling, social class, stress and environmental toxic exposition during gestation, pregnancy complications and familial psychiatric history. We found two principal components and used the scores of the components to subgroup patients. To avoid any possible grouping based on phenotypic established parameters such as IQ and severity we looked specifically into a group of homogeneous patients with severe disabilities, lowest IQ (IQ < 70), without clinical genetic syndrome. As for this population we would expect to find de novo and very rare variations with higher effects. We performed an exome analysis in a subsample to be able to check if any subgrouping will not be a consequence of this specific genetic component. Methylome analysis has been performed to validate and better explore subgroup differences.