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. 2019 Jul 2;9:9526. doi: 10.1038/s41598-019-45457-9

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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TADs in cortical neurons with strong core-periphery mesoscale structure are enriched for neuropsychiatric disease-associated single nucleotide variants. (A) Odds ratios representing the enrichment of schizophrenia-, OCD-, and ASD-associated common single nucleotide variants (SNVs) in TADs with strong and weak core-periphery structure compared to linkage disequilibrium size- and minor allele frequency-matched background SNVs (N = 100 sets of background SNVs). Pvalues, Fisher’s exact test. (B) Odds ratios representing the enrichment of schizophrenia-, OCD-, and ASD-associated common SNVs at core versus periphery nodes in TADs with strong core-periphery structure compared to linkage disequilibrium size- and minor allele frequency-matched background SNVs (N = 100 sets of background SNVs). Pvalues, Fisher’s exact test. (C) Observed/Expected heatmaps of neuropsychiatric daSNVs at core and periphery nodes in TADs with strong core-periphery structure. daSNV LD blocks are plotted below the heatmap (Supplementary Methods). (D) Schematic working model of the core-periphery network structure of the 3-D genome and our hypothesized model of the topological and functional consequences of daSNVs at core versus periphery nodes.