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. 2021 Aug 13;12:693142. doi: 10.3389/fimmu.2021.693142

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Copyright © 2021 Gokuladhas, Schierding, Golovina, Fadason and O’Sullivan

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Global overview of the genetic architecture of AIDs. (A) SNPs associated with each of 18 AiDs (D1 to D18) were analyzed through the CoDeS3D algorithm (Fadason et al., 2018). Briefly: (i) genes that are in physical contact with the SNPs (cis - located within 1 Mb distance, trans-intrachromosomal- located on the same chromosome but more than 1 Mb apart, and trans-interchromosomal - located on the different chromosomes) within the three-dimensional organization of the nucleus are identified; and (ii) SNP-gene pairs are queried through GTEx to identify those that overlap eQTL-eGene correlations. Lastly, the regulatory SNP-gene associations identified for each of 18 AiDs were consolidated to identify the genes (1), associated with pleiotropic SNPs only, (2) associated with pleiotropic & non-pleiotropic SNPs, or >2 non-pleiotropic SNPs associated with different AiDs and, (3) associated with non-pleiotropic SNPs only. (B) Summary of pleiotropic and non-pleiotropic SNPs (left) and their target genes (right) across 18 AiDs by proportion. Dotted lines indicate associations between categories of SNPs and genes. (C) The proportion of genes regulated in cis, trans (inter- and/or intra-chromosomal), or both cis and trans by the SNPs across 18 AiDs. (D) Trans-regulatory connections were enriched in single tissue. Proportion of genes was calculated as percentage total genes.