FGF23 and Immune Cell Signatures Causally Linked to Subarachnoid Hemorrhage: Evidence From Multi-Omics and Genetic Colocalization.
Inflammation and immune response significantly contribute to brain injury following subarachnoid hemorrhage (SAH), a severe neurological condition. This study employed Mendelian randomization, colocalization, and multi-omics analysis to examine potential causal connections between inflammatory proteins, immune cells, and SAH, aiming to elucidate its pathogenesis.
This study utilized publicly available data from genome-wide association studies (GWAS), including protein QTL (pQTL) and RNA sequencing data. Bidirectional two-sample Mendelian Randomization (MR) analysis was initially employed to evaluate the cause-and-effect relationships among inflammatory proteins, immune cells, and SAH. A comprehensive multi-omics approach, encompassing transcriptome, colocalization, mediation MR, was employed to identify specific inflammatory proteins, immune cells, and potential drug targets.
A causal relationship between five inflammatory proteins and SAH was identified through MR analysis (CD6, FGF23, TGFB-1, LIFR, and TGF-α). Moreover, a causal relationship with SAH was identified in 22 types of immune cells. Subsequent multi-omics analysis showed that FGF23 was a hub inflammatory protein, and its expression level was closely linked to the amount of CD4 Treg cells. Meta-analysis and replication studies identified FGF23 as a risk factor for SAH, with a colocalization score of 0.74.
This study successfully identified inflammatory proteins and immune cells associated with SAH, and revealed the complex genetic causality and drug targets of SAH.
This study utilized publicly available data from genome-wide association studies (GWAS), including protein QTL (pQTL) and RNA sequencing data. Bidirectional two-sample Mendelian Randomization (MR) analysis was initially employed to evaluate the cause-and-effect relationships among inflammatory proteins, immune cells, and SAH. A comprehensive multi-omics approach, encompassing transcriptome, colocalization, mediation MR, was employed to identify specific inflammatory proteins, immune cells, and potential drug targets.
A causal relationship between five inflammatory proteins and SAH was identified through MR analysis (CD6, FGF23, TGFB-1, LIFR, and TGF-α). Moreover, a causal relationship with SAH was identified in 22 types of immune cells. Subsequent multi-omics analysis showed that FGF23 was a hub inflammatory protein, and its expression level was closely linked to the amount of CD4 Treg cells. Meta-analysis and replication studies identified FGF23 as a risk factor for SAH, with a colocalization score of 0.74.
This study successfully identified inflammatory proteins and immune cells associated with SAH, and revealed the complex genetic causality and drug targets of SAH.
Authors
Shi Shi, Zhang Zhang, Yang Yang, Sun Sun, Wang Wang, Zhou Zhou, Hou Hou, Lin Lin, Zhang Zhang
View on Pubmed