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Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study
BACKGROUND: Type 2 diabetes mellitus (T2DM) and hypertension commonly coexist, and we presumed that T2DM might mediate the relationship between some shared risk factors and systolic blood pressure (SBP). METHODS: The causal association between T2DM and SBP was first confirmed using Mendelian randomi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800519/ https://www.ncbi.nlm.nih.gov/pubmed/36589843 http://dx.doi.org/10.3389/fendo.2022.1090867 |
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author | Hao, Xuezeng Li, Weixin Shi, Ruiqing Wang, Qiuhong |
author_facet | Hao, Xuezeng Li, Weixin Shi, Ruiqing Wang, Qiuhong |
author_sort | Hao, Xuezeng |
collection | PubMed |
description | BACKGROUND: Type 2 diabetes mellitus (T2DM) and hypertension commonly coexist, and we presumed that T2DM might mediate the relationship between some shared risk factors and systolic blood pressure (SBP). METHODS: The causal association between T2DM and SBP was first confirmed using Mendelian randomization (MR) analyses, and a two-step MR design was then used to test the causal mediating effect of T2DM on the relationship between 107 traits and SBP using summary statistics from genome-wide association studies. RESULTS: T2DM was causally associated with SBP. The univariable MR of the two-step causal mediation analyses suggested that 44 and 45 of the 107 traits had causal associations with T2DM and SBP, respectively. Five of the 27 traits that were significantly associated with both T2DM and SBP could not be reversely altered by T2DM and were included in the second step of the causal mediation analyses. The results indicated that most of the investigated traits causally altered SBP independent of T2DM, but the partial causal mediating effect of T2DM on the association between fasting insulin and SBP was successfully identified with a mediation proportion of 33.6%. CONCLUSIONS: Our study provides novel insights into the role of risk factors in the comorbidity of T2DM and high blood pressure, which is important for long-term disease prevention and management. |
format | Online Article Text |
id | pubmed-9800519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98005192022-12-31 Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study Hao, Xuezeng Li, Weixin Shi, Ruiqing Wang, Qiuhong Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Type 2 diabetes mellitus (T2DM) and hypertension commonly coexist, and we presumed that T2DM might mediate the relationship between some shared risk factors and systolic blood pressure (SBP). METHODS: The causal association between T2DM and SBP was first confirmed using Mendelian randomization (MR) analyses, and a two-step MR design was then used to test the causal mediating effect of T2DM on the relationship between 107 traits and SBP using summary statistics from genome-wide association studies. RESULTS: T2DM was causally associated with SBP. The univariable MR of the two-step causal mediation analyses suggested that 44 and 45 of the 107 traits had causal associations with T2DM and SBP, respectively. Five of the 27 traits that were significantly associated with both T2DM and SBP could not be reversely altered by T2DM and were included in the second step of the causal mediation analyses. The results indicated that most of the investigated traits causally altered SBP independent of T2DM, but the partial causal mediating effect of T2DM on the association between fasting insulin and SBP was successfully identified with a mediation proportion of 33.6%. CONCLUSIONS: Our study provides novel insights into the role of risk factors in the comorbidity of T2DM and high blood pressure, which is important for long-term disease prevention and management. Frontiers Media S.A. 2022-12-16 /pmc/articles/PMC9800519/ /pubmed/36589843 http://dx.doi.org/10.3389/fendo.2022.1090867 Text en Copyright © 2022 Hao, Li, Shi and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Hao, Xuezeng Li, Weixin Shi, Ruiqing Wang, Qiuhong Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study |
title | Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study |
title_full | Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study |
title_fullStr | Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study |
title_full_unstemmed | Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study |
title_short | Investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: A two-step Mendelian randomization study |
title_sort | investigating the causal mediating effect of type 2 diabetes on the relationship between traits and systolic blood pressure: a two-step mendelian randomization study |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800519/ https://www.ncbi.nlm.nih.gov/pubmed/36589843 http://dx.doi.org/10.3389/fendo.2022.1090867 |
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