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dc.contributor.authorMoksnes, Marta Riise
dc.contributor.authorRøsjø, Helge
dc.contributor.authorRichmond, Anne
dc.contributor.authorLyngbakken, Magnus N
dc.contributor.authorGraham, Sarah E
dc.contributor.authorWolford, Brooke N
dc.contributor.authorHansen, Ailin Falkmo
dc.contributor.authorGagliano Taliun, Sarah A
dc.contributor.authorLefaive, Jonathon
dc.contributor.authorRasheed, Humaira
dc.contributor.authorThomas, Laurent
dc.contributor.authorZhou, Wei
dc.contributor.authorAung, Nay
dc.contributor.authorSurakka, Ida
dc.contributor.authorDouville, Nicholas J
dc.contributor.authorCampbell, Archie
dc.contributor.authorPorteous, David J
dc.contributor.authorPetersen, Steffen E
dc.contributor.authorMunroe, Patricia B
dc.contributor.authorWelsh, Paul
dc.contributor.authorSattar, Naveed
dc.contributor.authorSmith, George Davey
dc.contributor.authorFritsche, Lars G
dc.contributor.authorNielsen, Jonas Bille
dc.contributor.authorÅsvold, Bjørn Olav
dc.contributor.authorHveem, Kristian
dc.contributor.authorHayward, Caroline
dc.contributor.authorWiller, Cristen J
dc.contributor.authorBrumpton, Ben M
dc.contributor.authorOmland, Torbjørn
dc.date.accessioned2022-03-21T15:36:19Z
dc.date.available2022-03-21T15:36:19Z
dc.date.created2021-12-02T11:32:03Z
dc.date.issued2021
dc.identifier.citationHuman Molecular Genetics. 2021, 30 (21), 2027-2039.en_US
dc.identifier.issn0964-6906
dc.identifier.urihttps://hdl.handle.net/11250/2986620
dc.description.abstractCirculating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes are unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study, and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further use two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction (AMI) and heart failure (HF). We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1688 phecodes and 83 continuous traits in UK Biobank showed associations between a genetic risk score for cTnI and cardiac arrhythmias, metabolic and anthropometric measures. Using two-sample Mendelian randomization, we confirmed the non-causal role of cTnI in AMI (5948 cases, 355 246 controls). We found indications for a causal role of cTnI in HF (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals). Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for AMI in the general population. Using genetically informed methods for causal inference helps inform the role and value of measuring cTnI in the general population.en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleGenome-wide association study of cardiac troponin i in the general populationen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.pagenumber2027-2039en_US
dc.source.volume30en_US
dc.source.journalHuman Molecular Geneticsen_US
dc.source.issue21en_US
dc.identifier.doi10.1093/hmg/ddab124
dc.identifier.cristin1963303
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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