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

Scheinhardt MO; Schnabel RB; Geelhoed B; Kuulasmaa K; Niiranen T; Havulinna AS; Blankenberg S; Salomaa V; Palosaari T; Jousilahti P; Zeller T; Borschel CS; Fouodo CJK

dc.contributor.authorScheinhardt MO
dc.contributor.authorSchnabel RB
dc.contributor.authorGeelhoed B
dc.contributor.authorKuulasmaa K
dc.contributor.authorNiiranen T
dc.contributor.authorHavulinna AS
dc.contributor.authorBlankenberg S
dc.contributor.authorSalomaa V
dc.contributor.authorPalosaari T
dc.contributor.authorJousilahti P
dc.contributor.authorZeller T
dc.contributor.authorBorschel CS
dc.contributor.authorFouodo CJK
dc.date.accessioned2022-10-28T13:18:10Z
dc.date.available2022-10-28T13:18:10Z
dc.identifier.urihttps://www.utupub.fi/handle/10024/164249
dc.description.abstractAims 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 poly-morphisms (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.
dc.language.isoen
dc.publisherOXFORD UNIV PRESS
dc.titleAssessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort
dc.identifier.urnURN:NBN:fi-fe2021042822317
dc.relation.volume22
dc.contributor.organizationfi=sisätautioppi|en=Internal Medicine|
dc.contributor.organization-code2607318
dc.converis.publication-id50449857
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/50449857
dc.format.pagerange1463
dc.format.pagerange1469
dc.identifier.jour-issn1099-5129
dc.okm.affiliatedauthorNiiranen, Teemu
dc.okm.discipline3121 Sisätauditfi_FI
dc.okm.discipline3121 Internal medicineen_GB
dc.okm.internationalcopublicationinternational co-publication
dc.okm.internationalityInternational publication
dc.okm.typeJournal article
dc.publisher.countryBritanniafi_FI
dc.publisher.countryUnited Kingdomen_GB
dc.publisher.country-codeGB
dc.relation.doi10.1093/europace/euaa158
dc.relation.ispartofjournalEP-Europace
dc.relation.issue10
dc.year.issued2020


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