Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes
Integrating expression quantitative trait loci (eQTL) data with genome-wide association studies (GWAS) enables the discovery of pleiotropic gene regulatory variants that influence a wide range of traits and disease susceptibilities. However, a comprehensive understanding of the distribution of pleio...
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Elsevier
2024-12-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S200103702400391X |
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| author | Aitor González Pascale Paul |
| author_facet | Aitor González Pascale Paul |
| author_sort | Aitor González |
| collection | DOAJ |
| description | Integrating expression quantitative trait loci (eQTL) data with genome-wide association studies (GWAS) enables the discovery of pleiotropic gene regulatory variants that influence a wide range of traits and disease susceptibilities. However, a comprehensive understanding of the distribution of pleiotropic QTLs across the genome and their phenotypic associations remain limited. In this study, we systematically annotated genetic variants associated with both trait variation and gene expression changes, focusing specifically on the unique characteristics of pleiotropic eQTLs. By integrating data from 127 eQTL studies and 417 traits from the IEU Open GWAS Project, we identified 476 pleiotropic eQTL variants affecting two or more distinct traits. Our analysis highlighted 5345 eQTL candidates potentially linked to gene expression changes across 293 GWAS traits. Notably, the 476 pleiotropic eQTLs associated with multiple trait categories were localized within a cumulative 2.5 Mbp genomic region. These pleiotropic eQTLs were enriched in enhancer regions and CTCF loops, influencing a larger number of genes in closer genomic proximity. Our findings reveal that pleiotropic eQTLs are concentrated within a small fraction of the genome and exhibit distinct molecular features. Colocalization results are accessible through an interactive web application and UCSC genome browser tracks at https://gwas2eqtl.tagc.univ-amu.fr/gwas2eqtl, facilitating the exploration of pleiotropic eQTLs and their roles in gene regulation and disease susceptibility. |
| format | Article |
| id | doaj-art-088cdd669e8a4aafae380a931c4e69ae |
| institution | OA Journals |
| issn | 2001-0370 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj-art-088cdd669e8a4aafae380a931c4e69ae2025-08-20T02:07:01ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-01234260427010.1016/j.csbj.2024.11.019Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genesAitor González0Pascale Paul1Corresponding author.; Aix-Marseille Univ, INSERM U1090, TAGC, Marseille 13288, FranceAix-Marseille Univ, INSERM U1090, TAGC, Marseille 13288, FranceIntegrating expression quantitative trait loci (eQTL) data with genome-wide association studies (GWAS) enables the discovery of pleiotropic gene regulatory variants that influence a wide range of traits and disease susceptibilities. However, a comprehensive understanding of the distribution of pleiotropic QTLs across the genome and their phenotypic associations remain limited. In this study, we systematically annotated genetic variants associated with both trait variation and gene expression changes, focusing specifically on the unique characteristics of pleiotropic eQTLs. By integrating data from 127 eQTL studies and 417 traits from the IEU Open GWAS Project, we identified 476 pleiotropic eQTL variants affecting two or more distinct traits. Our analysis highlighted 5345 eQTL candidates potentially linked to gene expression changes across 293 GWAS traits. Notably, the 476 pleiotropic eQTLs associated with multiple trait categories were localized within a cumulative 2.5 Mbp genomic region. These pleiotropic eQTLs were enriched in enhancer regions and CTCF loops, influencing a larger number of genes in closer genomic proximity. Our findings reveal that pleiotropic eQTLs are concentrated within a small fraction of the genome and exhibit distinct molecular features. Colocalization results are accessible through an interactive web application and UCSC genome browser tracks at https://gwas2eqtl.tagc.univ-amu.fr/gwas2eqtl, facilitating the exploration of pleiotropic eQTLs and their roles in gene regulation and disease susceptibility.http://www.sciencedirect.com/science/article/pii/S200103702400391XGenome-wide associations studies (GWAS), expression quantitative trait loci (eQTL)PleiotropyColocalization |
| spellingShingle | Aitor González Pascale Paul Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes Computational and Structural Biotechnology Journal Genome-wide associations studies (GWAS), expression quantitative trait loci (eQTL) Pleiotropy Colocalization |
| title | Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes |
| title_full | Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes |
| title_fullStr | Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes |
| title_full_unstemmed | Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes |
| title_short | Pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes |
| title_sort | pleiotropic expression quantitative trait loci are enriched in enhancers and transcription factor binding sites and impact more genes |
| topic | Genome-wide associations studies (GWAS), expression quantitative trait loci (eQTL) Pleiotropy Colocalization |
| url | http://www.sciencedirect.com/science/article/pii/S200103702400391X |
| work_keys_str_mv | AT aitorgonzalez pleiotropicexpressionquantitativetraitlociareenrichedinenhancersandtranscriptionfactorbindingsitesandimpactmoregenes AT pascalepaul pleiotropicexpressionquantitativetraitlociareenrichedinenhancersandtranscriptionfactorbindingsitesandimpactmoregenes |