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dc.contributor.authorSolomon, Terry
dc.contributor.authorSmith, Erin N.
dc.contributor.authorMatsui, Hiroko
dc.contributor.authorBrækkan, Sigrid Kufaas
dc.contributor.authorWilsgaard, Tom
dc.contributor.authorNjølstad, Inger
dc.contributor.authorMathiesen, Ellisiv B.
dc.contributor.authorHansen, John-Bjarne
dc.contributor.authorFrazer, Kelly A.
dc.date.accessioned2017-03-10T15:40:27Z
dc.date.available2017-03-10T15:40:27Z
dc.date.issued2016-06-21
dc.description.abstractBackground—Genetic variation can be used to study causal relationships between biomarkers and diseases. Here, we identify new common and rare genetic variants associated with cardiovascular-related protein levels (protein quantitative trait loci [pQTLs]). We functionally annotate these pQTLs, predict and experimentally confirm a novel molecular interaction, and determine which pQTLs are associated with diseases and physiological phenotypes. Methods and Results—As part of a larger case–control study of venous thromboembolism, serum levels of 51 proteins implicated in cardiovascular diseases were measured in 330 individuals from the Tromsø Study. Exonic genetic variation near each protein’s respective gene (cis) was identified using sequencing and arrays. Using single site and gene-based tests, we identified 27 genetic associations between pQTLs and the serum levels of 20 proteins: 14 associated with common variation in cis, of which 6 are novel (ie, not previously reported); 7 associations with rare variants in cis, of which 4 are novel; and 6 associations in trans. Of the 20 proteins, 15 were associated with single sites and 7 with rare variants. cis-pQTLs for kallikrein and F12 also show trans associations for proteins (uPAR, kininogen) known to be cleaved by kallikrein and with NTproBNP. We experimentally demonstrate that kallikrein can cleave proBNP (NTproBNP precursor) in vitro. Nine of the pQTLs have previously identified associations with 17 disease and physiological phenotypes. Conclusions—We have identified cis and trans genetic variation associated with the serum levels of 20 proteins and utilized these pQTLs to study molecular mechanisms underlying disease and physiological phenotypes.en_US
dc.descriptionPublished version. Source at <a href=http://dx.doi.org/10.1161/CIRCGENETICS.115.001327> http://dx.doi.org/10.1161/CIRCGENETICS.115.001327 </a>en_US
dc.identifier.citationSolomon, T. et.al.: Associations between Common and Rare Exonic Genetic Variants and Serum Levels of 20 Cardiovascular-Related Proteins: The Tromsø Study. Circulation: Cardiovascular Genetics. 2016;9(4):375-383en_US
dc.identifier.cristinIDFRIDAID 1395217
dc.identifier.doi10.1161/CIRCGENETICS.115.001327
dc.identifier.issn1942-325X
dc.identifier.issn1942-3268
dc.identifier.urihttps://hdl.handle.net/10037/10554
dc.language.isoengen_US
dc.publisherAmerican Heart Associationen_US
dc.relation.journalCirculation: Cardiovascular Genetics
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714en_US
dc.subjectbiomarkeren_US
dc.subjectcoronary artery diseaseen_US
dc.subjectexomeen_US
dc.subjecthumanen_US
dc.subjectproteinen_US
dc.subjectvenous thromboembolismen_US
dc.titleAssociations between Common and Rare Exonic Genetic Variants and Serum Levels of 20 Cardiovascular-Related Proteins: The Tromsø Studyen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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