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","contactForAccess":"Please fill out the <a href=\"https://www.umcutrecht.nl/en/data-request-form-umc-utrecht\">request form</a>.","fileAccessRequest":false,"metadataBlocks":{"citation":{"displayName":"Citation Metadata","name":"citation","fields":[{"typeName":"title","multiple":false,"typeClass":"primitive","value":"Common variants associated with OSMR expression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans"},{"typeName":"author","multiple":true,"typeClass":"compound","value":[{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Sander W. van der Laan"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Central Diagnostics Laboratory, University Medical Center Utrecht"},"authorIdentifierScheme":{"typeName":"authorIdentifierScheme","multiple":false,"typeClass":"controlledVocabulary","value":"ORCID"},"authorIdentifier":{"typeName":"authorIdentifier","multiple":false,"typeClass":"primitive","value":"0000-0001-6888-1404"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Daniëlle van Keulen"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Laboratory of Experimental Cardiology, University Medical Center Utrecht"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Ian D. van Koeverden"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Laboratory of Experimental Cardiology, University Medical Center Utrecht"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Arjan Boltjes"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Central Diagnostics Laboratory, University Medical Center Utrecht"},"authorIdentifierScheme":{"typeName":"authorIdentifierScheme","multiple":false,"typeClass":"controlledVocabulary","value":"ORCID"},"authorIdentifier":{"typeName":"authorIdentifier","multiple":false,"typeClass":"primitive","value":"0000-0002-6338-051X"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Hans M.G. Princen"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"TNO-Metabolic Health Research, Gaubius Laboratory"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Alain J. van Gool"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Translational Metabolic Laboratory, Radboudumc"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Gert Jan de Borst"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Department of Vascular Surgery, University Medical Center Utrecht"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Folkert W. Asselbergs"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht"},"authorIdentifierScheme":{"typeName":"authorIdentifierScheme","multiple":false,"typeClass":"controlledVocabulary","value":"ORCID"},"authorIdentifier":{"typeName":"authorIdentifier","multiple":false,"typeClass":"primitive","value":"000-0002-1692-8669"}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Dennie Tempel"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Quorics B.V."}},{"authorName":{"typeName":"authorName","multiple":false,"typeClass":"primitive","value":"Gerard Pasterkamp"},"authorAffiliation":{"typeName":"authorAffiliation","multiple":false,"typeClass":"primitive","value":"Central Diagnostics Laboratory, University Medical Center Utrecht"}}]},{"typeName":"datasetContact","multiple":true,"typeClass":"compound","value":[{"datasetContactName":{"typeName":"datasetContactName","multiple":false,"typeClass":"primitive","value":"Sander W. van der Laan"},"datasetContactAffiliation":{"typeName":"datasetContactAffiliation","multiple":false,"typeClass":"primitive","value":"University Medical Center Utrecht"}},{"datasetContactName":{"typeName":"datasetContactName","multiple":false,"typeClass":"primitive","value":"Division Datamanager"},"datasetContactAffiliation":{"typeName":"datasetContactAffiliation","multiple":false,"typeClass":"primitive","value":"University Medical Center Utrecht"}}]},{"typeName":"dsDescription","multiple":true,"typeClass":"compound","value":[{"dsDescriptionValue":{"typeName":"dsDescriptionValue","multiple":false,"typeClass":"primitive","value":"This dataset pertains to the data used for the article \"van Keulen D et al. <em>Common variants associated with <em>OSMR</em> expression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans.</em> 2021\"; below the abstract.\n<br>\n<br>\n<b>Background and aims</b> <br>\nOncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in OSM and its receptors, OSMR and LIFR, on overall plaque vulnerability, plaque phenotype, intraplaque <em>OSMR</em> and <em>LIFR</em> expression, coronary artery calcification burden and cardiovascular disease susceptibility.\n<br>\n<br>\n<b>Methods and results</b> <br>\nWe queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreased <em>OSMR</em> expression and that rs10491509 (A allele) was associated with increased <em>LIFR</em> expression in arterial tissues. No variant was significantly associated with OSM expression.\n<br>\n<br>\nWe associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β=0.118 ± s.e.=0.040, p=3.00×10<sup>-3</sup>, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β=0.248 ± s.e.=0.088, p=4.66×10<sup>-3</sup>, C allele) and collagen content (β=-0.259 ± s.e.=0.095, p=6.22×10<sup>-3</sup>, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaque <em>OSMR</em> expression. Neither was intraplaque <em>OSMR</em> expression associated with plaque vulnerability and no known <em>OSMR</em> eQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in the <em>LIFR</em> locus.\n\n<br>\n<br>\n<b>Conclusions  </b><br>\nOur study suggests that rs1316887 in the <em>OSMR</em> locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.\n<br>\n<br>\n<b>Competing Interest Statement </b><br>\nDvK is employed by Quorics B.V., and DT is employed by SkylineDx B.V and Quorics B.V. Quorics B.V. and SkylineDx B.V. had no part whatsoever in the conception, design, or execution of this study, nor the preparation and contents of this manuscript.\n<br>\n<br>\n<b>Scripts</b><br>\nScripts are posted at GitHub <a href=\"https://github.com/swvanderlaan/2019_vankeulen_d_osmr\" target=\"_blank\">https://github.com/swvanderlaan/2019_vankeulen_d_osmr</a>."}}]},{"typeName":"subject","multiple":true,"typeClass":"controlledVocabulary","value":["Medicine, Health and Life Sciences"]},{"typeName":"keyword","multiple":true,"typeClass":"compound","value":[{"keywordValue":{"typeName":"keywordValue","multiple":false,"typeClass":"primitive","value":"atherosclerosis"}},{"keywordValue":{"typeName":"keywordValue","multiple":false,"typeClass":"primitive","value":"OSMR"}},{"keywordValue":{"typeName":"keywordValue","multiple":false,"typeClass":"primitive","value":"eQTL"}},{"keywordValue":{"typeName":"keywordValue","multiple":false,"typeClass":"primitive","value":"genetics"}}]},{"typeName":"publication","multiple":true,"typeClass":"compound","value":[{"publicationCitation":{"typeName":"publicationCitation","multiple":false,"typeClass":"primitive","value":"<b>Front. Cardiovasc. Med.</b></br>\nCommon variants associated with OSMR expression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans\nD. van Keulen, I.D. van Koeverden, A. Boltjes, H.M.G. Princen, A.J. van Gool, G.J. de Borst, F.W. Asselbergs, D. Tempel, G. Pasterkamp, S.W. van der Laan\nFront. Cardiovasc. Med., 20 April 2021 8:239; doi: <a href=\"https://doi.org/10.3389/fcvm.2021.658915\" target=\"_blank\">https://doi.org/10.3389/fcvm.2021.658915</a>"},"publicationIDType":{"typeName":"publicationIDType","multiple":false,"typeClass":"controlledVocabulary","value":"doi"},"publicationIDNumber":{"typeName":"publicationIDNumber","multiple":false,"typeClass":"primitive","value":"10.3389/fcvm.2021.658915"},"publicationURL":{"typeName":"publicationURL","multiple":false,"typeClass":"primitive","value":"https://doi.org/10.3389/fcvm.2021.658915"}},{"publicationCitation":{"typeName":"publicationCitation","multiple":false,"typeClass":"primitive","value":"<b>bioRxiv preprint</b></br>\nCommon variants associated with OSMR expression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans\nD. van Keulen, I.D. van Koeverden, A. Boltjes, H.M.G. Princen, A.J. van Gool, G.J. de Borst, F.W. Asselbergs, D. Tempel, G. Pasterkamp, S.W. van der Laan\nbioRxiv 576793; doi: <a href=\"https://doi.org/10.1101/576793\" target=\"_blank\">https://doi.org/10.1101/576793</a>"},"publicationIDType":{"typeName":"publicationIDType","multiple":false,"typeClass":"controlledVocabulary","value":"doi"},"publicationIDNumber":{"typeName":"publicationIDNumber","multiple":false,"typeClass":"primitive","value":"10.1101/576793"},"publicationURL":{"typeName":"publicationURL","multiple":false,"typeClass":"primitive","value":"https://doi.org/10.1101/576793"}}]},{"typeName":"depositor","multiple":false,"typeClass":"primitive","value":"Sander W. van der Laan"},{"typeName":"dateOfDeposit","multiple":false,"typeClass":"primitive","value":"2021-04-08"},{"typeName":"software","multiple":true,"typeClass":"compound","value":[{"softwareName":{"typeName":"softwareName","multiple":false,"typeClass":"primitive","value":"GitHub"},"softwareVersion":{"typeName":"softwareVersion","multiple":false,"typeClass":"primitive","value":"https://github.com/swvanderlaan/2019_vankeulen_d_osmr"}}]}]},"biomedical":{"displayName":"Life Sciences Metadata","name":"biomedical","fields":[{"typeName":"studyDesignType","multiple":true,"typeClass":"controlledVocabulary","value":["Cross Sectional","Cohort Study"]},{"typeName":"studyFactorType","multiple":true,"typeClass":"controlledVocabulary","value":["Age","Biomarkers","Disease State","Genetic Characteristics","Platform","Sex"]},{"typeName":"studyAssayOrganism","multiple":true,"typeClass":"controlledVocabulary","value":["Homo sapiens"]},{"typeName":"studyAssayMeasurementType","multiple":true,"typeClass":"controlledVocabulary","value":["histology","SNP analysis","transcription profiling (RNA-Seq)"]},{"typeName":"studyAssayTechnologyType","multiple":true,"typeClass":"controlledVocabulary","value":["DNA microarray","nucleotide sequencing","Other"]}]},"dansDataVaultMetadata":{"displayName":"Data Vault Metadata","name":"dansDataVaultMetadata","fields":[{"typeName":"dansDataversePid","multiple":false,"typeClass":"primitive","value":"doi:10.34894/0RB5IZ"},{"typeName":"dansDataversePidVersion","multiple":false,"typeClass":"primitive","value":"3.0"},{"typeName":"dansBagId","multiple":false,"typeClass":"primitive","value":"urn:uuid:ef530ccb-de84-4ef2-95c1-bd786853c8e7"},{"typeName":"dansNbn","multiple":false,"typeClass":"primitive","value":"urn:nbn:nl:ui:13-ec8848b1-deb9-404a-a1aa-f051bb20a0d1"}]}},"files":[{"description":"METC Approval of the Athero-Express Biobank Study","label":"20020410_Approval_Protocol_TME_Athero-Express_Biobank_Study.pdf","restricted":true,"version":1,"datasetVersionId":24389,"dataFile":{"id":192690,"persistentId":"","filename":"20020410_Approval_Protocol_TME_Athero-Express_Biobank_Study.pdf","contentType":"application/pdf","friendlyType":"Adobe PDF","filesize":61663,"description":"METC Approval of the Athero-Express Biobank Study","storageIdentifier":"surf://store:17c6fb7545a-9129eac9ee1e","rootDataFileId":-1,"checksum":{"type":"SHA-1","value":"7af1184782ed6d4c33f554077390c88f0ab184b4"},"tabularData":false,"creationDate":"2021-10-11","publicationDate":"2021-11-19","lastUpdateTime":"2022-10-19T13:16:58Z","fileAccessRequest":false}},{"description":"DMP of the Athero-Express Biobank Study","label":"20211007_DMP_Athero-Express_Biobank_Study.pdf","restricted":true,"version":1,"datasetVersionId":24389,"dataFile":{"id":192689,"persistentId":"","filename":"20211007_DMP_Athero-Express_Biobank_Study.pdf","contentType":"application/pdf","friendlyType":"Adobe PDF","filesize":64158,"description":"DMP of the Athero-Express Biobank Study","storageIdentifier":"surf://store:17c6fb75669-d9228561c695","rootDataFileId":-1,"checksum":{"type":"SHA-1","value":"a733a0cddb4a49961748170591890e5aa47494d1"},"tabularData":false,"creationDate":"2021-10-11","publicationDate":"2021-11-19","lastUpdateTime":"2022-10-19T13:16:58Z","fileAccessRequest":false}},{"description":"OXFORD-style .gen file containing probabilities for the variants used.","label":"aegs_combo_1kGp3GoNL5_RAW_chr5.OSMR.gen","restricted":true,"version":1,"datasetVersionId":24389,"dataFile":{"id":94575,"persistentId":"","filename":"aegs_combo_1kGp3GoNL5_RAW_chr5.OSMR.gen","contentType":"application/octet-stream","friendlyType":"Unknown","filesize":73310,"description":"OXFORD-style .gen file containing probabilities for the variants used.","storageIdentifier":"surf://store:17956f8aea1-c510f93fbbaf","rootDataFileId":-1,"checksum":{"type":"SHA-1","value":"a9a9c38d0ff094868eccca51ee94e28b76c50774"},"tabularData":false,"creationDate":"2021-05-10","publicationDate":"2021-11-19","lastUpdateTime":"2022-10-19T13:16:58Z","fileAccessRequest":false}},{"description":"Sample file matching VCF.GZ and .GEN files. 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