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...
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ftpubmed:oai:pubmedcentral.nih.gov:9978757 2023-05-15T17:42:42+02:00 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 2023-02-14 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978757/ https://doi.org/10.1136/bmjmed-2022-000157 en eng BMJ Publishing Group http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978757/ http://dx.doi.org/10.1136/bmjmed-2022-000157 © 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/. BMJ Med Research Text 2023 ftpubmed https://doi.org/10.1136/bmjmed-2022-000157 2023-03-19T01:37:57Z 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 ... Text Northern Finland PubMed Central (PMC) BMJ Medicine 2 1 e000157 |
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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 |
topic_facet |
Research |
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 ... |
format |
Text |
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 |
title |
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_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_sort |
interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
publisher |
BMJ Publishing Group |
publishDate |
2023 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978757/ https://doi.org/10.1136/bmjmed-2022-000157 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
BMJ Med |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978757/ http://dx.doi.org/10.1136/bmjmed-2022-000157 |
op_rights |
© 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/. |
op_doi |
https://doi.org/10.1136/bmjmed-2022-000157 |
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BMJ Medicine |
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