Abstract
J Thromb Haemost. 2024 Sep 17:S1538-7836(24)00544-0. doi: 10.1016/j.jtha.2024.08.021. Online ahead of print.
ABSTRACT
BACKGROUND: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published GWAS, highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.
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 (CHARGE) 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 two traits and Genotype-Tissue Expression (GTEx) 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.
PMID:39299614 | DOI:10.1016/j.jtha.2024.08.021
UK DRI Authors
