Integration Analysis of mA-SNPs and eQTLs Associated With Sepsis Reveals Platelet Degranulation and Infection are Mediated by mA mRNA Methylation.

Sepsis is a major threat with high mortality rate for critically ill patients. Response to pathogen infection by the host immune system is a key biological process involved in the onset and development of sepsis. Heterogeneous host genome variation, especially single nucleotide polymorphisms (SNPs), has long been suggested to contribute to differences in disease progression. However, the function of SNPs located in non-coding regions remains to be elucidated. Recently, mA mRNA modification levels were revealed to differ at SNPs. As mA is a crucial regulator of gene expression, these SNPs might control genes by changing the mA level on mRNA. To investigate the potential role of mA SNPs in sepsis, we integrated mA-SNP and expression quantitative trait loci (eQTLs) data. Analysis revealed 15,720 mA-cis-eQTLs and 381 mA-trans-eQTLs associated with sepsis. We identified 1321 genes as locations of mA-cis-eQTLs. These were enriched in platelet degranulation and infection pathways, which are vital for the pathophysiological process of sepsis. We conclude that mA modification of mRNA plays a very important role in sepsis, with mA-cis-eQTLs potentially having the most effect on individual variation in sepsis progression.