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Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population
BACKGROUND: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to bet...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403965/ https://www.ncbi.nlm.nih.gov/pubmed/37543566 http://dx.doi.org/10.1186/s12864-023-09532-w |
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author | Rouskas, Konstantinos Katsareli, Efthymia A. Amerikanou, Charalampia Dimopoulos, Alexandros C. Glentis, Stavros Kalantzi, Alexandra Skoulakis, Anargyros Panousis, Nikolaos Ongen, Halit Bielser, Deborah Planchon, Alexandra Romano, Luciana Harokopos, Vaggelis Reczko, Martin Moulos, Panagiotis Griniatsos, Ioannis Diamantis, Theodoros Dermitzakis, Emmanouil T. Ragoussis, Jiannis Dedoussis, George Dimas, Antigone S. |
author_facet | Rouskas, Konstantinos Katsareli, Efthymia A. Amerikanou, Charalampia Dimopoulos, Alexandros C. Glentis, Stavros Kalantzi, Alexandra Skoulakis, Anargyros Panousis, Nikolaos Ongen, Halit Bielser, Deborah Planchon, Alexandra Romano, Luciana Harokopos, Vaggelis Reczko, Martin Moulos, Panagiotis Griniatsos, Ioannis Diamantis, Theodoros Dermitzakis, Emmanouil T. Ragoussis, Jiannis Dedoussis, George Dimas, Antigone S. |
author_sort | Rouskas, Konstantinos |
collection | PubMed |
description | BACKGROUND: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource. RESULTS: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue. CONCLUSIONS: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-023-09532-w. |
format | Online Article Text |
id | pubmed-10403965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104039652023-08-06 Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population Rouskas, Konstantinos Katsareli, Efthymia A. Amerikanou, Charalampia Dimopoulos, Alexandros C. Glentis, Stavros Kalantzi, Alexandra Skoulakis, Anargyros Panousis, Nikolaos Ongen, Halit Bielser, Deborah Planchon, Alexandra Romano, Luciana Harokopos, Vaggelis Reczko, Martin Moulos, Panagiotis Griniatsos, Ioannis Diamantis, Theodoros Dermitzakis, Emmanouil T. Ragoussis, Jiannis Dedoussis, George Dimas, Antigone S. BMC Genomics Research BACKGROUND: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource. RESULTS: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue. CONCLUSIONS: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-023-09532-w. BioMed Central 2023-08-05 /pmc/articles/PMC10403965/ /pubmed/37543566 http://dx.doi.org/10.1186/s12864-023-09532-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Rouskas, Konstantinos Katsareli, Efthymia A. Amerikanou, Charalampia Dimopoulos, Alexandros C. Glentis, Stavros Kalantzi, Alexandra Skoulakis, Anargyros Panousis, Nikolaos Ongen, Halit Bielser, Deborah Planchon, Alexandra Romano, Luciana Harokopos, Vaggelis Reczko, Martin Moulos, Panagiotis Griniatsos, Ioannis Diamantis, Theodoros Dermitzakis, Emmanouil T. Ragoussis, Jiannis Dedoussis, George Dimas, Antigone S. Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population |
title | Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population |
title_full | Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population |
title_fullStr | Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population |
title_full_unstemmed | Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population |
title_short | Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population |
title_sort | identifying novel regulatory effects for clinically relevant genes through the study of the greek population |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403965/ https://www.ncbi.nlm.nih.gov/pubmed/37543566 http://dx.doi.org/10.1186/s12864-023-09532-w |
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