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The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study
OBJECTIVE: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. DESIGN: Bi-directional Mendelian randomisation study. SETTING: Genome-wide association studies from t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978757/ https://www.ncbi.nlm.nih.gov/pubmed/36936266 http://dx.doi.org/10.1136/bmjmed-2022-000157 |
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author | Karhunen, Ville Gill, Dipender Huang, Jian Bouras, Emmanouil Malik, Rainer Ponsford, Mark J Ahola-Olli, Ari Papadopoulou, Areti Palaniswamy, Saranya Sebert, Sylvain Wielscher, Matthias Auvinen, Juha Veijola, Juha Herzig, Karl-Heinz Timonen, Markku Keinänen-Kiukaanniemi, Sirkka Dichgans, Martin Salmi, Marko Jalkanen, Sirpa Lehtimäki, Terho Salomaa, Veikko Raitakari, Olli Jones, Simon A Hovingh, G Kees Tsilidis, Konstantinos K Järvelin, Marjo-Riitta Dehghan, Abbas |
author_facet | Karhunen, Ville Gill, Dipender Huang, Jian Bouras, Emmanouil Malik, Rainer Ponsford, Mark J Ahola-Olli, Ari Papadopoulou, Areti Palaniswamy, Saranya Sebert, Sylvain Wielscher, Matthias Auvinen, Juha Veijola, Juha Herzig, Karl-Heinz Timonen, Markku Keinänen-Kiukaanniemi, Sirkka Dichgans, Martin Salmi, Marko Jalkanen, Sirpa Lehtimäki, Terho Salomaa, Veikko Raitakari, Olli Jones, Simon A Hovingh, G Kees Tsilidis, Konstantinos K Järvelin, Marjo-Riitta Dehghan, Abbas |
author_sort | Karhunen, Ville |
collection | PubMed |
description | OBJECTIVE: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. DESIGN: Bi-directional Mendelian randomisation study. SETTING: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits. PARTICIPANTS: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits. INTERVENTIONS: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking). MAIN OUTCOME METHODS: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated. RESULTS: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evidence for causal relations (mendelian randomisation P<0.0011) were noted between circulating cytokines, including a key role of vascular endothelial growth factor on influencing the concentrations of 10 other cytokines. Both mendelian randomisation (P<0.05) and colocalisation (posterior probability >0.5) suggested that coronary artery disease risk is increased by higher concentrations of circulating tumour necrosis factor related apoptosis-inducing ligand (TRAIL), interleukin-1 receptor antagonist (IL1RA), and macrophage colony-stimulating factor (MCSF). CONCLUSION: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes. |
format | Online Article Text |
id | pubmed-9978757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-99787572023-03-16 The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study Karhunen, Ville Gill, Dipender Huang, Jian Bouras, Emmanouil Malik, Rainer Ponsford, Mark J Ahola-Olli, Ari Papadopoulou, Areti Palaniswamy, Saranya Sebert, Sylvain Wielscher, Matthias Auvinen, Juha Veijola, Juha Herzig, Karl-Heinz Timonen, Markku Keinänen-Kiukaanniemi, Sirkka Dichgans, Martin Salmi, Marko Jalkanen, Sirpa Lehtimäki, Terho Salomaa, Veikko Raitakari, Olli Jones, Simon A Hovingh, G Kees Tsilidis, Konstantinos K Järvelin, Marjo-Riitta Dehghan, Abbas BMJ Med Research OBJECTIVE: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. DESIGN: Bi-directional Mendelian randomisation study. SETTING: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits. PARTICIPANTS: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits. INTERVENTIONS: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking). MAIN OUTCOME METHODS: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated. RESULTS: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evidence for causal relations (mendelian randomisation P<0.0011) were noted between circulating cytokines, including a key role of vascular endothelial growth factor on influencing the concentrations of 10 other cytokines. Both mendelian randomisation (P<0.05) and colocalisation (posterior probability >0.5) suggested that coronary artery disease risk is increased by higher concentrations of circulating tumour necrosis factor related apoptosis-inducing ligand (TRAIL), interleukin-1 receptor antagonist (IL1RA), and macrophage colony-stimulating factor (MCSF). CONCLUSION: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes. BMJ Publishing Group 2023-02-14 /pmc/articles/PMC9978757/ /pubmed/36936266 http://dx.doi.org/10.1136/bmjmed-2022-000157 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Karhunen, Ville Gill, Dipender Huang, Jian Bouras, Emmanouil Malik, Rainer Ponsford, Mark J Ahola-Olli, Ari Papadopoulou, Areti Palaniswamy, Saranya Sebert, Sylvain Wielscher, Matthias Auvinen, Juha Veijola, Juha Herzig, Karl-Heinz Timonen, Markku Keinänen-Kiukaanniemi, Sirkka Dichgans, Martin Salmi, Marko Jalkanen, Sirpa Lehtimäki, Terho Salomaa, Veikko Raitakari, Olli Jones, Simon A Hovingh, G Kees Tsilidis, Konstantinos K Järvelin, Marjo-Riitta Dehghan, Abbas The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
title | The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
title_full | The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
title_fullStr | The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
title_full_unstemmed | The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
title_short | The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
title_sort | interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978757/ https://www.ncbi.nlm.nih.gov/pubmed/36936266 http://dx.doi.org/10.1136/bmjmed-2022-000157 |
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