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Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort

AIMS: Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with nat...

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Autores principales: Geelhoed, Bastiaan, Börschel, Christin S, Niiranen, Teemu, Palosaari, Tarja, Havulinna, Aki S, Fouodo, Césaire J K, Scheinhardt, Markus O, Blankenberg, Stefan, Jousilahti, Pekka, Kuulasmaa, Kari, Zeller, Tanja, Salomaa, Veikko, Schnabel, Renate B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544535/
https://www.ncbi.nlm.nih.gov/pubmed/32830215
http://dx.doi.org/10.1093/europace/euaa158
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author Geelhoed, Bastiaan
Börschel, Christin S
Niiranen, Teemu
Palosaari, Tarja
Havulinna, Aki S
Fouodo, Césaire J K
Scheinhardt, Markus O
Blankenberg, Stefan
Jousilahti, Pekka
Kuulasmaa, Kari
Zeller, Tanja
Salomaa, Veikko
Schnabel, Renate B
author_facet Geelhoed, Bastiaan
Börschel, Christin S
Niiranen, Teemu
Palosaari, Tarja
Havulinna, Aki S
Fouodo, Césaire J K
Scheinhardt, Markus O
Blankenberg, Stefan
Jousilahti, Pekka
Kuulasmaa, Kari
Zeller, Tanja
Salomaa, Veikko
Schnabel, Renate B
author_sort Geelhoed, Bastiaan
collection PubMed
description AIMS: Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. METHODS AND RESULTS: N-terminal pro B-type natriuretic peptide (NT-proBNP) (N = 6669), B-type natriuretic peptide (BNP) (N = 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N = 6813) were measured in the FINRISK 1997 cohort. N = 30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. CONCLUSION: In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.
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spelling pubmed-75445352020-10-15 Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort Geelhoed, Bastiaan Börschel, Christin S Niiranen, Teemu Palosaari, Tarja Havulinna, Aki S Fouodo, Césaire J K Scheinhardt, Markus O Blankenberg, Stefan Jousilahti, Pekka Kuulasmaa, Kari Zeller, Tanja Salomaa, Veikko Schnabel, Renate B Europace Clinical Research AIMS: Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. METHODS AND RESULTS: N-terminal pro B-type natriuretic peptide (NT-proBNP) (N = 6669), B-type natriuretic peptide (BNP) (N = 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N = 6813) were measured in the FINRISK 1997 cohort. N = 30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. CONCLUSION: In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms. Oxford University Press 2020-08-23 /pmc/articles/PMC7544535/ /pubmed/32830215 http://dx.doi.org/10.1093/europace/euaa158 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research
Geelhoed, Bastiaan
Börschel, Christin S
Niiranen, Teemu
Palosaari, Tarja
Havulinna, Aki S
Fouodo, Césaire J K
Scheinhardt, Markus O
Blankenberg, Stefan
Jousilahti, Pekka
Kuulasmaa, Kari
Zeller, Tanja
Salomaa, Veikko
Schnabel, Renate B
Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
title Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
title_full Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
title_fullStr Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
title_full_unstemmed Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
title_short Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
title_sort assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a mendelian randomization study in the finrisk cohort
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544535/
https://www.ncbi.nlm.nih.gov/pubmed/32830215
http://dx.doi.org/10.1093/europace/euaa158
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