Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation
Introduction: Plasma proteins play essential roles in myocardial infarction (MI) and atrial fibrillation (AF) ; however, it remains unknown whether the two disorders share causal plasma proteins. Methods: The present study utilizes cis-protein quantitative trait loci (cis-pQTLs) for 4,719 plasma pro...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tabriz University of Medical Sciences
2024-12-01
|
| Series: | Journal of Cardiovascular and Thoracic Research |
| Subjects: | |
| Online Access: | https://jcvtr.tbzmed.ac.ir/PDF/jcvtr-16-249.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850250793081372672 |
|---|---|
| author | Hadi Charati Ahmad Hamta |
| author_facet | Hadi Charati Ahmad Hamta |
| author_sort | Hadi Charati |
| collection | DOAJ |
| description | Introduction: Plasma proteins play essential roles in myocardial infarction (MI) and atrial fibrillation (AF) ; however, it remains unknown whether the two disorders share causal plasma proteins. Methods: The present study utilizes cis-protein quantitative trait loci (cis-pQTLs) for 4,719 plasma proteins to assess their causality on MI and AF. Results: Two-sample Mendelian randomization (MR) identifies 21 and 9 plasma proteins for MI and AF, respectively (FDR P<0.05), with plasminogen (PLG) being a commonly protective factor against both diseases. Multi-trait MR suggests that PLG is also protective against coronary atherosclerosis. PheWAS analysis identifies associations of six cis-pQTLs with both MI and AF, i.e., rs11751347 (PLG), rs11591147 (PCSK9), rs77347777 (ITIH4), rs936228 (ULK3), rs2261033 (AIF1V), and rs2711897 (BDH2). Furthermore, interactions exist among the causal plasma proteins, with PLG directly interacting with multiple others. Drug-gene databases suggest that PLG activators, such as Urokinase, Reteplase, Streptokinase, Alteplase, Anistreplase, Tenecteplase, Desmoteplase, and Defibrotide sodium may serve as common therapeutic drugs for MI and AF. Conclusion: Our study provides a causal inference of human plasma proteins in MI and AF. Several of the identified proteins and single nucleotide polymorphisms (sNPs) exert pleiotropic effects on other cardiometabolic phenotypes, indicating their crucial roles in the pathology of cardiovascular disease (CVD). Our study provides new insights into the shared causality and drugs for MI and AF. |
| format | Article |
| id | doaj-art-6d73ddb652504657b2c2558cb7b8ee04 |
| institution | OA Journals |
| issn | 2008-5117 2008-6830 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Journal of Cardiovascular and Thoracic Research |
| spelling | doaj-art-6d73ddb652504657b2c2558cb7b8ee042025-08-20T01:58:05ZengTabriz University of Medical SciencesJournal of Cardiovascular and Thoracic Research2008-51172008-68302024-12-0116424925710.34172/jcvtr.33269jcvtr-33269Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillationHadi Charati0Ahmad Hamta1Department of Biology, Faculty of Sciences, Arak University, Arak, IranDepartment of Biology, Faculty of Sciences, Arak University, Arak, IranIntroduction: Plasma proteins play essential roles in myocardial infarction (MI) and atrial fibrillation (AF) ; however, it remains unknown whether the two disorders share causal plasma proteins. Methods: The present study utilizes cis-protein quantitative trait loci (cis-pQTLs) for 4,719 plasma proteins to assess their causality on MI and AF. Results: Two-sample Mendelian randomization (MR) identifies 21 and 9 plasma proteins for MI and AF, respectively (FDR P<0.05), with plasminogen (PLG) being a commonly protective factor against both diseases. Multi-trait MR suggests that PLG is also protective against coronary atherosclerosis. PheWAS analysis identifies associations of six cis-pQTLs with both MI and AF, i.e., rs11751347 (PLG), rs11591147 (PCSK9), rs77347777 (ITIH4), rs936228 (ULK3), rs2261033 (AIF1V), and rs2711897 (BDH2). Furthermore, interactions exist among the causal plasma proteins, with PLG directly interacting with multiple others. Drug-gene databases suggest that PLG activators, such as Urokinase, Reteplase, Streptokinase, Alteplase, Anistreplase, Tenecteplase, Desmoteplase, and Defibrotide sodium may serve as common therapeutic drugs for MI and AF. Conclusion: Our study provides a causal inference of human plasma proteins in MI and AF. Several of the identified proteins and single nucleotide polymorphisms (sNPs) exert pleiotropic effects on other cardiometabolic phenotypes, indicating their crucial roles in the pathology of cardiovascular disease (CVD). Our study provides new insights into the shared causality and drugs for MI and AF.https://jcvtr.tbzmed.ac.ir/PDF/jcvtr-16-249.pdfatrial fibrillationcis-pqtldrug targetsmendelian randomizationmyocardial infarction |
| spellingShingle | Hadi Charati Ahmad Hamta Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation Journal of Cardiovascular and Thoracic Research atrial fibrillation cis-pqtl drug targets mendelian randomization myocardial infarction |
| title | Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation |
| title_full | Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation |
| title_fullStr | Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation |
| title_full_unstemmed | Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation |
| title_short | Mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation |
| title_sort | mendelian randomization reveals plasminogen as a common therapeutic target for myocardial infarction and atrial fibrillation |
| topic | atrial fibrillation cis-pqtl drug targets mendelian randomization myocardial infarction |
| url | https://jcvtr.tbzmed.ac.ir/PDF/jcvtr-16-249.pdf |
| work_keys_str_mv | AT hadicharati mendelianrandomizationrevealsplasminogenasacommontherapeutictargetformyocardialinfarctionandatrialfibrillation AT ahmadhamta mendelianrandomizationrevealsplasminogenasacommontherapeutictargetformyocardialinfarctionandatrialfibrillation |