Autism spectrum conditions are neurodevelopmental conditions that entail social- communication difficulties, unusually narrow interests and difficulties adjusting to unexpected change. While the role of NRXN1 has been established in regulating normal synaptic function and physiology, its contribution to the aetiology of autism is only now emerging. However, to fully understand how NRXN1 influences neuronal phenotypes, synaptic and functional changes a reliable and relevant human cellular model is needed. In this thesis I have used induced neurons derived from induced pluripotent stem cells (iPSC) using the OPTi-OX system to study the impact of NRXN1 mutations on excitatory glutamatergic neurons. I specifically study the molecular, morphological and functional changes caused by 1) induced mutations in CRISPR-edited cell lines; and 2) iPSCs derived from autistic individuals with NRXN1 mutations. The hypothesis is that intronic mutations in the patient lines and exonic mutations in the mutant lines have distinct effects on molecular, morphological and functional activity of glutamatergic neurons. NRXN1-patient neurons displayed distinct patterns of NRXN1 isoform expression. Patient line 211_NXM had a significantly higher levels of NRXN1 expression compared to patient line 092_NXF. 211_NXM neurons also displayed significantly higher firing rates as determined by MEA recordings. Conversely, patient line 092-NXF had NRXN1 expression and neurons with aberrant neurite outgrowth. I also generated four different NRXN1- mtant lines. Each NRXN1-mutant line exhibited distinct expression levels of NRXN1 and its isoforms. Furthermore, each line displayed disrupted neurite outgrowth to varying degrees. Finally, RNA-Seq analysis revealed notable upregulation for genes enriched for cell adhesion biological functions in the patient lines and chemical synaptic transmission pathways in the mutant lines. Of particular interest were enrichment of differentially regulated genes in collagen and cadherin family genes, consistent with alterations in adhesion properties in neurons with NRXN1-mutations. The strength of the thesis lie in the technological advancements of forward programming and iPSC technologies, however further experiments with a bigger sample size might be required to validate and support the findings described. Thus, these data contribute to our overall understanding of how NRXN1 may contribute to the aetiology of autism and demonstrates the complexity of its effects. In the second part of this thesis, I investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year-olds, by conducting a methylome-wide association study (MWAS). Using methylation data for autism in peripheral tissues, we did not identify a significant concordance in effect direction of CpGs with p value < 10−4 in the SCDC MWAS (binomial sign test, p value > 0.5). In contrast, using methylation data for autism from post-mortem brain tissues, a significant concordance in effect direction of CpGs with a p value < 10−4 in the SCDC MWAS (binomial sign test, p value = 0.004) was reported. Supporting this, I observe an enrichment for genes that are dysregulated in the post- mortem autism brain (one-sided Wilcoxon rank-sum test, p value=6.22×10−5). Finally, integrating genome-wide association study (GWAS) data for autism (n = 46,350) with mQTL maps from cord-blood (n = 771), we demonstrate that mQTLs of CpGs associated with SCDC scores at p value thresholds of 0.01 and 0.005 are significantly shifted toward lower p values in the GWAS for autism (p < 5 × 10−3). Addition support for this using a GWAS of SCDC demonstrate a lack of enrichment in a GWAS of Alzheimer’s disease. These results highlight the shared cross-tissue methylation architecture of autism and autistic traits and demonstrate that mQTLs associated with differences in DNA methylation associated with childhood autistic traits are enriched for common genetic variants associated with autism and autistic traits.