PT - JOURNAL ARTICLE AU - D. van Keulen AU - I. D. van Koeverden AU - A. Boltjes AU - H. M. G. Princen AU - A. J. van Gool AU - G.J. de Borst AU - F.W. Asselbergs AU - D. Tempel AU - G. Pasterkamp AU - S.W. van der Laan TI - Common variants associated with <em>OSMR</em> expression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans AID - 10.1101/576793 DP - 2020 Jan 01 TA - bioRxiv PG - 576793 4099 - http://biorxiv.org/content/early/2020/07/30/576793.short 4100 - http://biorxiv.org/content/early/2020/07/30/576793.full AB - Background and aims Oncostatin 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 OSMR and LIFR expression, coronary artery calcification burden and cardiovascular disease susceptibility.Methods and results We queried Genotype-Tissue Expression data and found rs13168867 (C allele) and rs10491509 (A allele) to be associated with decreased OSMR and increased LIFR expression in arterial tissue respectively. No variant was significantly associated with OSM expression.We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. rs13168867 was associated with an increased overall plaque vulnerability (β=0.118 ± s.e.=0.040, p=3.00×10−3, C allele) and although not significant after correction for multiple testing, it showed strongest associations with intraplaque fat (β=0.248 ± s.e.=0.088, C allele) and collagen content (β=-0.259 ± s.e.=0.095, C allele). rs13168867 was not associated with intraplaque OSMR expression. Neither was intraplaque OSMR expression associated with plaque vulnerability and no known OSMR eQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in the LIFR locus.Conclusions Our study suggests that genetically decreased arterial OSMR expression contributes to increased carotid plaque vulnerability. However, the OSM signaling pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility as none of the investigated variants associated with cardiovascular diseases.Competing Interest StatementDvK 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.