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Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges
Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomis...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036461/ https://www.ncbi.nlm.nih.gov/pubmed/36786839 http://dx.doi.org/10.1007/s00125-023-05879-7 |
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author | Yuan, Shuai Merino, Jordi Larsson, Susanna C. |
author_facet | Yuan, Shuai Merino, Jordi Larsson, Susanna C. |
author_sort | Yuan, Shuai |
collection | PubMed |
description | Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains a slide of the figure for download available at 10.1007/s00125-023-05879-7. |
format | Online Article Text |
id | pubmed-10036461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-100364612023-03-25 Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges Yuan, Shuai Merino, Jordi Larsson, Susanna C. Diabetologia Review Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains a slide of the figure for download available at 10.1007/s00125-023-05879-7. Springer Berlin Heidelberg 2023-02-14 2023 /pmc/articles/PMC10036461/ /pubmed/36786839 http://dx.doi.org/10.1007/s00125-023-05879-7 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/) . |
spellingShingle | Review Yuan, Shuai Merino, Jordi Larsson, Susanna C. Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges |
title | Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges |
title_full | Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges |
title_fullStr | Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges |
title_full_unstemmed | Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges |
title_short | Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges |
title_sort | causal factors underlying diabetes risk informed by mendelian randomisation analysis: evidence, opportunities and challenges |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036461/ https://www.ncbi.nlm.nih.gov/pubmed/36786839 http://dx.doi.org/10.1007/s00125-023-05879-7 |
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