Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S de Vries
{"title":"循环纤维蛋白原和 C 反应蛋白水平的双变量全基因组关联研究。","authors":"Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S de Vries","doi":"10.1016/j.jtha.2024.08.021","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.</p><p><strong>Objectives: </strong>To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.</p><p><strong>Methods: </strong>We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (n = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (n = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data.</p><p><strong>Results: </strong>We identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near ZZZ3, NR1I2, RP11-72L22.1, MICU1, ARL14EP, SOCS2, and PGM5. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS.</p><p><strong>Conclusion: </strong>Bivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bivariate genome-wide association study of circulating fibrinogen and C-reactive protein levels.\",\"authors\":\"Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S de Vries\",\"doi\":\"10.1016/j.jtha.2024.08.021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.</p><p><strong>Objectives: </strong>To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.</p><p><strong>Methods: </strong>We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (n = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (n = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data.</p><p><strong>Results: </strong>We identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near ZZZ3, NR1I2, RP11-72L22.1, MICU1, ARL14EP, SOCS2, and PGM5. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS.</p><p><strong>Conclusion: </strong>Bivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.</p>\",\"PeriodicalId\":17326,\"journal\":{\"name\":\"Journal of Thrombosis and Haemostasis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtha.2024.08.021\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtha.2024.08.021","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Bivariate genome-wide association study of circulating fibrinogen and C-reactive protein levels.
Background: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.
Objectives: To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.
Methods: We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (n = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (n = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data.
Results: We identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near ZZZ3, NR1I2, RP11-72L22.1, MICU1, ARL14EP, SOCS2, and PGM5. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS.
Conclusion: Bivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.
期刊介绍：
The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community.
Types of Publications:
The journal publishes a variety of content, including:
Original research reports
State-of-the-art reviews
Brief reports
Case reports
Invited commentaries on publications in the Journal
Forum articles
Correspondence
Announcements
Scope of Contributions:
Editors invite contributions from both fundamental and clinical domains. These include:
Basic manuscripts on blood coagulation and fibrinolysis
Studies on proteins and reactions related to thrombosis and haemostasis
Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms
Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases
Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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