The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study
Abstract 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 studi...
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BMJ
2023
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Open Polar |
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Jultika - University of Oulu repository |
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English |
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Cardiology Epidemiology Genetics |
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Cardiology Epidemiology Genetics Karhunen, V. (Ville) Gill, D. (Dipender) Huang, J. (Jian) Bouras, E. (Emmanouil) Malik, R. (Rainer) Ponsford, M. J. (Mark J.) Ahola-Olli, A. (Ari) Papadopoulou, A. (Areti) Palaniswamy, S. (Saranya) Sebert, S. (Sylvain) Wielscher, M. (Matthias) Auvinen, J. (Juha) Veijola, J. (Juha) Herzig, K.-H. (Karl-Heinz) Timonen, M. (Markku) Keinänen-Kiukaanniemi, S. (Sirkka) Dichgans, M. (Martin) Salmi, M. (Marko) Jalkanen, S. (Sirpa) Lehtimäki, T. (Terho) Salomaa, V. (Veikko) Raitakari, O. (Olli) Jones, S. A. (Simon A.) Hovingh, G. K. (G. Kees) Tsilidis, K. K. (Konstantinos K.) Järvelin, M.-R. (Marjo-Riitta) Dehghan, A. (Abbas) The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study |
topic_facet |
Cardiology Epidemiology Genetics |
description |
Abstract 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 |
Article in Journal/Newspaper |
author |
Karhunen, V. (Ville) Gill, D. (Dipender) Huang, J. (Jian) Bouras, E. (Emmanouil) Malik, R. (Rainer) Ponsford, M. J. (Mark J.) Ahola-Olli, A. (Ari) Papadopoulou, A. (Areti) Palaniswamy, S. (Saranya) Sebert, S. (Sylvain) Wielscher, M. (Matthias) Auvinen, J. (Juha) Veijola, J. (Juha) Herzig, K.-H. (Karl-Heinz) Timonen, M. (Markku) Keinänen-Kiukaanniemi, S. (Sirkka) Dichgans, M. (Martin) Salmi, M. (Marko) Jalkanen, S. (Sirpa) Lehtimäki, T. (Terho) Salomaa, V. (Veikko) Raitakari, O. (Olli) Jones, S. A. (Simon A.) Hovingh, G. K. (G. Kees) Tsilidis, K. K. (Konstantinos K.) Järvelin, M.-R. (Marjo-Riitta) Dehghan, A. (Abbas) |
author_facet |
Karhunen, V. (Ville) Gill, D. (Dipender) Huang, J. (Jian) Bouras, E. (Emmanouil) Malik, R. (Rainer) Ponsford, M. J. (Mark J.) Ahola-Olli, A. (Ari) Papadopoulou, A. (Areti) Palaniswamy, S. (Saranya) Sebert, S. (Sylvain) Wielscher, M. (Matthias) Auvinen, J. (Juha) Veijola, J. (Juha) Herzig, K.-H. (Karl-Heinz) Timonen, M. (Markku) Keinänen-Kiukaanniemi, S. (Sirkka) Dichgans, M. (Martin) Salmi, M. (Marko) Jalkanen, S. (Sirpa) Lehtimäki, T. (Terho) Salomaa, V. (Veikko) Raitakari, O. (Olli) Jones, S. A. (Simon A.) Hovingh, G. K. (G. Kees) Tsilidis, K. K. (Konstantinos K.) Järvelin, M.-R. (Marjo-Riitta) Dehghan, A. (Abbas) |
author_sort |
Karhunen, V. (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 |
publishDate |
2023 |
url |
http://urn.fi/urn:nbn:fi-fe20230912122836 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_relation |
info:eu-repo/grantAgreement/EC/H2020/848158/EU/Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity/EarlyCause info:eu-repo/grantAgreement/EC/H2020/825762/EU/Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways/EDCMET info:eu-repo/grantAgreement/EC/H2020/633595/EU/Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging/DYNAHEALTH info:eu-repo/grantAgreement/EC/H2020/733206/EU/Early-life stressors and LifeCycle health/LIFECYCLE info:eu-repo/grantAgreement/EC/H2020/643774/EU/Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes/iHealth-T2D info:eu-repo/grantAgreement/EC/H2020/874739/EU/Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases/LONGITOOLS info:eu-repo/grantAgreement/EC/H2020/824989/EU/A federated FAIR platform enabling large-scale analysis of high-value cohort data connecting Europe and Canada in personalized health/EUCAN-Connect |
op_rights |
info:eu-repo/semantics/openAccess © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. 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/. https://creativecommons.org/licenses/by/4.0/ |
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1779317996219531264 |
spelling |
ftunivoulu:oai:oulu.fi:nbnfi-fe20230912122836 2023-10-09T21:54:26+02:00 The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study Karhunen, V. (Ville) Gill, D. (Dipender) Huang, J. (Jian) Bouras, E. (Emmanouil) Malik, R. (Rainer) Ponsford, M. J. (Mark J.) Ahola-Olli, A. (Ari) Papadopoulou, A. (Areti) Palaniswamy, S. (Saranya) Sebert, S. (Sylvain) Wielscher, M. (Matthias) Auvinen, J. (Juha) Veijola, J. (Juha) Herzig, K.-H. (Karl-Heinz) Timonen, M. (Markku) Keinänen-Kiukaanniemi, S. (Sirkka) Dichgans, M. (Martin) Salmi, M. (Marko) Jalkanen, S. (Sirpa) Lehtimäki, T. (Terho) Salomaa, V. (Veikko) Raitakari, O. (Olli) Jones, S. A. (Simon A.) Hovingh, G. K. (G. Kees) Tsilidis, K. K. (Konstantinos K.) Järvelin, M.-R. (Marjo-Riitta) Dehghan, A. (Abbas) 2023 application/pdf http://urn.fi/urn:nbn:fi-fe20230912122836 eng eng BMJ info:eu-repo/grantAgreement/EC/H2020/848158/EU/Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity/EarlyCause info:eu-repo/grantAgreement/EC/H2020/825762/EU/Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways/EDCMET info:eu-repo/grantAgreement/EC/H2020/633595/EU/Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging/DYNAHEALTH info:eu-repo/grantAgreement/EC/H2020/733206/EU/Early-life stressors and LifeCycle health/LIFECYCLE info:eu-repo/grantAgreement/EC/H2020/643774/EU/Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes/iHealth-T2D info:eu-repo/grantAgreement/EC/H2020/874739/EU/Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases/LONGITOOLS info:eu-repo/grantAgreement/EC/H2020/824989/EU/A federated FAIR platform enabling large-scale analysis of high-value cohort data connecting Europe and Canada in personalized health/EUCAN-Connect info:eu-repo/semantics/openAccess © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ. 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/. https://creativecommons.org/licenses/by/4.0/ Cardiology Epidemiology Genetics info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2023 ftunivoulu 2023-09-13T23:00:06Z Abstract 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 ... Article in Journal/Newspaper Northern Finland Jultika - University of Oulu repository |