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Diabetes risk loci-associated pathways are shared across metabolic tissues
AIMS/HYPOTHESIS: Numerous genome-wide association studies have been performed to understand the influence of genetic variation on type 2 diabetes etiology. Many identified risk variants are located in non-coding and intergenic regions, which complicates understanding of how genes and their downstrea...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107144/ https://www.ncbi.nlm.nih.gov/pubmed/35568807 http://dx.doi.org/10.1186/s12864-022-08587-5 |
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author | Bouland, Gerard A. Beulens, Joline W. J. Nap, Joey van der Slik, Arno R. Zaldumbide, Arnaud ’t Hart, Leen M. Slieker, Roderick C. |
author_facet | Bouland, Gerard A. Beulens, Joline W. J. Nap, Joey van der Slik, Arno R. Zaldumbide, Arnaud ’t Hart, Leen M. Slieker, Roderick C. |
author_sort | Bouland, Gerard A. |
collection | PubMed |
description | AIMS/HYPOTHESIS: Numerous genome-wide association studies have been performed to understand the influence of genetic variation on type 2 diabetes etiology. Many identified risk variants are located in non-coding and intergenic regions, which complicates understanding of how genes and their downstream pathways are influenced. An integrative data approach will help to understand the mechanism and consequences of identified risk variants. METHODS: In the current study we use our previously developed method CONQUER to overlap 403 type 2 diabetes risk variants with regulatory, expression and protein data to identify tissue-shared disease-relevant mechanisms. RESULTS: One SNP rs474513 was found to be an expression-, protein- and metabolite QTL. Rs474513 influenced LPA mRNA and protein levels in the pancreas and plasma, respectively. On the pathway level, in investigated tissues most SNPs linked to metabolism. However, in eleven of the twelve tissues investigated nine SNPs were linked to differential expression of the ribosome pathway. Furthermore, seven SNPs were linked to altered expression of genes linked to the immune system. Among them, rs601945 was found to influence multiple HLA genes, including HLA-DQA2, in all twelve tissues investigated. CONCLUSION: Our results show that in addition to the classical metabolism pathways, other pathways may be important to type 2 diabetes that show a potential overlap with type 1 diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-08587-5. |
format | Online Article Text |
id | pubmed-9107144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91071442022-05-15 Diabetes risk loci-associated pathways are shared across metabolic tissues Bouland, Gerard A. Beulens, Joline W. J. Nap, Joey van der Slik, Arno R. Zaldumbide, Arnaud ’t Hart, Leen M. Slieker, Roderick C. BMC Genomics Research AIMS/HYPOTHESIS: Numerous genome-wide association studies have been performed to understand the influence of genetic variation on type 2 diabetes etiology. Many identified risk variants are located in non-coding and intergenic regions, which complicates understanding of how genes and their downstream pathways are influenced. An integrative data approach will help to understand the mechanism and consequences of identified risk variants. METHODS: In the current study we use our previously developed method CONQUER to overlap 403 type 2 diabetes risk variants with regulatory, expression and protein data to identify tissue-shared disease-relevant mechanisms. RESULTS: One SNP rs474513 was found to be an expression-, protein- and metabolite QTL. Rs474513 influenced LPA mRNA and protein levels in the pancreas and plasma, respectively. On the pathway level, in investigated tissues most SNPs linked to metabolism. However, in eleven of the twelve tissues investigated nine SNPs were linked to differential expression of the ribosome pathway. Furthermore, seven SNPs were linked to altered expression of genes linked to the immune system. Among them, rs601945 was found to influence multiple HLA genes, including HLA-DQA2, in all twelve tissues investigated. CONCLUSION: Our results show that in addition to the classical metabolism pathways, other pathways may be important to type 2 diabetes that show a potential overlap with type 1 diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-08587-5. BioMed Central 2022-05-14 /pmc/articles/PMC9107144/ /pubmed/35568807 http://dx.doi.org/10.1186/s12864-022-08587-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 Bouland, Gerard A. Beulens, Joline W. J. Nap, Joey van der Slik, Arno R. Zaldumbide, Arnaud ’t Hart, Leen M. Slieker, Roderick C. Diabetes risk loci-associated pathways are shared across metabolic tissues |
title | Diabetes risk loci-associated pathways are shared across metabolic tissues |
title_full | Diabetes risk loci-associated pathways are shared across metabolic tissues |
title_fullStr | Diabetes risk loci-associated pathways are shared across metabolic tissues |
title_full_unstemmed | Diabetes risk loci-associated pathways are shared across metabolic tissues |
title_short | Diabetes risk loci-associated pathways are shared across metabolic tissues |
title_sort | diabetes risk loci-associated pathways are shared across metabolic tissues |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107144/ https://www.ncbi.nlm.nih.gov/pubmed/35568807 http://dx.doi.org/10.1186/s12864-022-08587-5 |
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