دورية أكاديمية
Plasma proteomics to identify drug targets for ischemic heart disease
| العنوان: | Plasma proteomics to identify drug targets for ischemic heart disease |
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| المؤلفون: | Mazidi, M, Wright, N, Yao, P, Kartsonaki, C, Millwood, I, Fry, H, Said, S, Pozarickij, A, Chen, Y, Avery, D, Du, H, Schmidt, D, Yang, L, Hill, M, Holmes, M, Peto, R, Collins, R, Bennett, D, Walters, R, Clarke, R, Chen, Z |
| المساهمون: | Group, China Kadoorie Biobank Collaborative |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | Background Integrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases. Objectives The purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments. Methods We conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease. We measured 1,463 proteins in the stored baseline samples using the OLINK EXPLORE panel. Cox regression yielded adjusted HRs for IHD associated with individual proteins after accounting for multiple testing. Moreover, cis-protein quantitative loci (pQTLs) identified for proteins in genome-wide association studies of CKB and of UK Biobank were used as instrumental variables in separate 2-sample Mendelian randomization (MR) studies involving global CARDIOGRAM+C4D consortium (210,842 IHD cases and 1,378,170 controls). Results Overall 361 proteins were significantly associated at false discovery rate <0.05 with risk of IHD (349 positively, 12 inversely) in CKB, including N-terminal prohormone of brain natriuretic peptide and proprotein convertase subtilisin/kexin type 9. Of these 361 proteins, 212 had cis-pQTLs in CKB, and MR analyses of 198 variants in CARDIOGRAM+C4D identified 13 proteins that showed potentially causal associations with IHD. Independent MR analyses of 307 cis-pQTLs identified in Europeans replicated associations for 4 proteins (FURIN, proteinase-activated receptor-1, Asialoglycoprotein receptor-1, and matrix metalloproteinase-3). Further downstream analyses showed that FURIN, which is highly expressed in endothelial cells, is a potential novel target and matrix metalloproteinase-3 a potential repurposing target for IHD. Conclusions Integrated analyses of proteomic and genetic data in Chinese and European ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://ora.ox.ac.uk/objects/uuid:f526e870-aea0-4d2e-a49e-c03849dde7beTest; https://doi.org/10.1016/j.jacc.2023.09.804Test |
| DOI: | 10.1016/j.jacc.2023.09.804 |
| الإتاحة: | https://doi.org/10.1016/j.jacc.2023.09.804Test https://ora.ox.ac.uk/objects/uuid:f526e870-aea0-4d2e-a49e-c03849dde7beTest |
| حقوق: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| رقم الانضمام: | edsbas.5396DB6E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jacc.2023.09.804 |
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