Fig. 3.

Euclidean hot spot analysis. a Violin plot representing each of the 11 EH, showing distance of domain-to-nuclear centroid. Scaled circles represent the number of domains found in each EH. Red color represents EHs no.7 and no.10 harboring the largest number of domains, as indicated. b Violin plot representing rpmks gene expression levels per EH, circle plots showing number of genes (N_genes) and number of transcribed non-coding elements (N_TNE) per EH, as indicated. Note that EH no. 7 and no. 10 (red) represent transcriptionally active domain clusters. c–e In silico chrom3D models of MDN spatial genome, red beads = EH-specific domains, c EH no. 7, d pink beads = cluster C (from Fig. 2e) domains shared among EH no. 7 and no. 10, and e EH no. 10. Circos plot interactomes for (c, right panel) EH no.7 and (d, right panel) cluster C^(7,10) and (e, right panel) EH no. 10, showing for each participating chromosome the location of (red tick marks) risk SNPs and (red lines) Hi-C Pro called chromosomal contacts reciprocally interconnecting BMI-to-SCZ risk variants at 40 kb resolution, including position of selected target genes. “Background chromosomal contacts” (blue) mark “BMI risk variant-to-rest of EH” contacts and (green) “SCZ risk variant-to-rest of EH” contacts, using BMI and SCZ index SNPs (Additional file 2: Table S4). f Permutation analysis probability density plot. The likelihood of cross disorder BMI-to-SCZ reciprocal interactions associated to significant brain cis-eQTLs (called at FDR < 10⁻⁸) was performed by comparing the association of randomized cross-disorder interactions (10,000 permutations) over the observed overlap. g Representative brain cis-eQTLs Manhattan plots shown for three domains from EH no. 10. Red shaded fields mark sequences fulfilling each of the following three conditions: (i) harboring both SCZ and BMI risk polymorphisms, (ii) anchored in cross-disorder chromosomal contact within the EH, and (iii) harboring significant brain cis-eQTLs. As an example, highlighted by red connector lines scaled to the ICED interaction frequency, interactions anchored in chr1611p2B2-B3/B4-B5 locus implicated in weight regulation and neurodevelopment [87] to disease-relevant associated genes SREBF1, SREBF2, and EP300