Some DEGs are downstream of signaling pathways perturbed in the SZ neurons, but the dysregulation of others may be due to disrupted spatial chromosomal interactions, which occur in the nucleus under normal physiological conditions, juxtaposing distal genes for efficient co-regulation [90–94]. By analyzing Hi-C data generated to assess chromatin folding and packaging in the nuclei of human lymphoblastoid cell lines [95], we identified three genomic regions with the strongest physical interaction with 22q11.2: 4p16, 8q24 and 6p21 (mean Pearson correlation coefficient > 0.4). Among the three, only 6p21 was statistically enriched for differentially expressed genes (χ2 test p-value = 0.01) (Fig. 4). Interestingly, this region has recently been linked with 16p11.2 deletion syndrome, a genetic cause for ASD [96]. 6p21 contains a number of genes involved in immune responses, including the human leukocyte antigen (HLA) gene cluster. As mentioned earlier, one of the HLA genes residing in this region, HLA-A, was among the small group of DEGs that remained statistically significant at a genome-wide scale. It should also be pointed out that the most robust GWAS (genome wide association studies)
