Nurlan Kerimov, Ralf Tambets, James D Hayhurst, Ida Rahu, Peep Kolberg, Uku Raudvere, Ivan Kuzmin, Anshika Chowdhary, Andreas Vija, Hans J Teras, Masahiro Kanai, Jacob Ulirsch, Mina Ryten, John Hardy, Sebastian Guelfi, Daniah Trabzuni, Sarah Kim-Hellmuth, William Rayner, Hilary Finucane, Hedi Peterson, Abayomi Mosaku, Helen Parkinson, Kaur Alasoo
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We have also implemented Leafcutter to directly identify splice-junction usage QTLs in all RNA sequencing datasets. Finally, to improve the interpretability of transcript-level QTLs, we have developed static QTL coverage plots that visualise the association between the genotype and average RNA sequencing read coverage in the region for all 1.7 million fine mapped associations. To illustrate the utility of these updates to the eQTL Catalogue, we performed colocalisation analysis between vitamin D levels in the UK Biobank and all molecular QTLs in the eQTL Catalogue. Although most GWAS loci colocalised both with eQTLs and transcript-level QTLs, we found that visual inspection could sometimes be used to distinguish primary splicing QTLs from those that appear to be secondary consequences of large-effect gene expression QTLs. While these visually confirmed primary splicing QTLs explain just 6/53 of the colocalising signals, they are significantly less pleiotropic than eQTLs and identify a prioritised causal gene in 4/6 cases.</p>","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538656/pdf/","citationCount":"1","resultStr":"{\"title\":\"eQTL Catalogue 2023: New datasets, X chromosome QTLs, and improved detection and visualisation of transcript-level QTLs.\",\"authors\":\"Nurlan Kerimov, Ralf Tambets, James D Hayhurst, Ida Rahu, Peep Kolberg, Uku Raudvere, Ivan Kuzmin, Anshika Chowdhary, Andreas Vija, Hans J Teras, Masahiro Kanai, Jacob Ulirsch, Mina Ryten, John Hardy, Sebastian Guelfi, Daniah Trabzuni, Sarah Kim-Hellmuth, William Rayner, Hilary Finucane, Hedi Peterson, Abayomi Mosaku, Helen Parkinson, Kaur Alasoo\",\"doi\":\"10.1371/journal.pgen.1010932\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs). 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eQTL Catalogue 2023: New datasets, X chromosome QTLs, and improved detection and visualisation of transcript-level QTLs.
The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs). We are continuously updating the resource to further increase its utility for interpreting genetic associations with complex traits. Over the past two years, we have increased the number of uniformly processed studies from 21 to 31 and added X chromosome QTLs for 19 compatible studies. We have also implemented Leafcutter to directly identify splice-junction usage QTLs in all RNA sequencing datasets. Finally, to improve the interpretability of transcript-level QTLs, we have developed static QTL coverage plots that visualise the association between the genotype and average RNA sequencing read coverage in the region for all 1.7 million fine mapped associations. To illustrate the utility of these updates to the eQTL Catalogue, we performed colocalisation analysis between vitamin D levels in the UK Biobank and all molecular QTLs in the eQTL Catalogue. Although most GWAS loci colocalised both with eQTLs and transcript-level QTLs, we found that visual inspection could sometimes be used to distinguish primary splicing QTLs from those that appear to be secondary consequences of large-effect gene expression QTLs. While these visually confirmed primary splicing QTLs explain just 6/53 of the colocalising signals, they are significantly less pleiotropic than eQTLs and identify a prioritised causal gene in 4/6 cases.
期刊介绍:
PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill).
Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.