Integration Analysis of m6A-SNPs and eQTLs Associated With Sepsis Reveals Platelet Degranulation and Staphylococcus aureus Infection are Mediated by m6A 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, m(6)A mRNA modification levels were revealed to differ at SNPs. As m(6)A is a crucial regulator of gene expression, these SNPs might control genes by changing the m(6)A level on mRNA. To investigate the potential role of m(6)A SNPs in sepsis, we integrated m(6)A-SNP and expression quantitative trait loci (eQTLs) data. Analysis revealed 15,720 m(6)A-cis-eQTLs and 381 m(6)A-trans-eQTLs associated with sepsis. We identified 1321 genes as locations of m(6)A-cis-eQTLs. These were enriched in platelet degranulation and Staphylococcus aureus infection pathways, which are vital for the pathophysiological process of sepsis. We conclude that m(6)A modification of mRNA plays a very important role in sepsis, with m(6)A-cis-eQTLs potentially having the most effect on individual variation in sepsis progression.