Unveiling Shared Genetic Links between Blood Cell Traits and Cardiovascular Diseases
Kong, L.; Yao, K.; Zheng, L.; Zhao, Y.; Chen, M.; Han, Z.; Wang, Q.; Feng, Q.; Lv, Y.; Zhang, B.; Li, F.
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Previous studies have linked blood cell traits (BCTs) to cardiovascular diseases (CVDs) risks, but the common genetic mechanisms underlying heritable phenotypes remain unclear. Our study used multiple analytical approaches including single nucleotide polymorphisms, genes, pathways, and protein targets to reveal common genetic elements. We confirmed both genome-wide and local genetic associations between BCTs and CVDs, identifying key pleiotropic loci and genes contributing to these links. Specifically, ALDH2, MAPKAPK5, and ACAD10, all located at 12q24.1, are associated with leukocyte-CVD traits. TNFSF12 at 17p13.1 and ABO at 9q34.2 correlate with platelet-CVD traits, while ZNF664 and CCDC92, also at 12q24.1, are linked to erythrocyte-CVD traits. Our findings also highlight multiple key trait-specific pathways mediating these phenotypic associations and potential therapeutic targets that may inform future clinical interventions. These insights significantly advance our understanding of the genetic interplay between BCTs and CVDs, underscoring the importance of focusing on BCTs to prevent cardiovascular conditions. HighlightsO_LIThere were wide genetic correlation and overlap between BCT and CVD. C_LIO_LIKey pleiotropic loci and genes for three BCT-CVD trait pairs were identified. C_LIO_LIKey signature-specific pathways mediating the BCTs-CVDs association were identified. C_LIO_LIPotential therapeutic targets for BCTs-CVDs were identified. C_LI eTOC blurbKong et al. report extensive genetic correlations and genetic overlaps between blood cell traits (BCTs) and cardiovascular diseases (CVDs), revealing key pleiotropic loci and genes contributing to these associations, as well as multiple trait-specific pathways mediating these phenotypic associations. Potential therapeutic targets to inform future clinical interventions were also identified, laying the foundation for understanding the genetic interactions between BCTs and CVDs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=142 HEIGHT=200 SRC="FIGDIR/small/24315926v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@98a11dorg.highwire.dtl.DTLVardef@79b4c5org.highwire.dtl.DTLVardef@4b2926org.highwire.dtl.DTLVardef@7a937b_HPS_FORMAT_FIGEXP M_FIG C_FIG
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