Garrido Martín, Diego, 1992-Borsari, Beatrice, 1992-Calvo, Miquel (Calvo Llorca)Reverter, FerranGuigó Serra, Roderic2021-03-102021-03-102021Garrido-Martín D, Borsari B, Calvo M, Reverter F, Guigó R. Identification and analysis of splicing quantitative trait loci across multiple tissues in the human genome. Nat Commun. 2021; 12(1):727. DOI: 10.1038/s41467-020-20578-22041-1723http://hdl.handle.net/10230/46710Alternative splicing (AS) is a fundamental step in eukaryotic mRNA biogenesis. Here, we develop an efficient and reproducible pipeline for the discovery of genetic variants that affect AS (splicing QTLs, sQTLs). We use it to analyze the GTEx dataset, generating a comprehensive catalog of sQTLs in the human genome. Downstream analysis of this catalog provides insight into the mechanisms underlying splicing regulation. We report that a core set of sQTLs is shared across multiple tissues. sQTLs often target the global splicing pattern of genes, rather than individual splicing events. Many also affect the expression of the same or other genes, uncovering regulatory loci that act through different mechanisms. sQTLs tend to be located in post-transcriptionally spliced introns, which would function as hotspots for splicing regulation. While many variants affect splicing patterns by altering the sequence of splice sites, many more modify the binding sites of RNA-binding proteins. Genetic variants affecting splicing can have a stronger phenotypic impact than those affecting gene expression.application/pdfeng© The Author(s) 2021. 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/.Identification and analysis of splicing quantitative trait loci across multiple tissues in the human genomeinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-020-20578-2Computational biology and bioinformaticsTranscriptomicsinfo:eu-repo/semantics/openAccess