A Potential Causal Association of Pyroglutamine with Systemic Lupus Erythematosus Revealed by a Mendelian Randomization Analysis
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Abstract
Pyroglutamate has been reported to be associated with many diseases such atherosclerosis, esophageal cancer, and COVID-19. However, it is still unclear about the role of blood pyroglutamate in Systemic Lupus Erythematosus (SLE). The present study used a two-sample Mendelian Randomization (MR) study to identify the potential causal association of pyroglutamine levels with SLE risk. Pyroglutamine-associated genetic Instrumental Variables (IVs) were chosen from the largest Genome-wide Association Studies (GWAS) for blood pyroglutamine-levels. The largest GWAS for SLE was employed to identify the potential causal association of blood pyroglutamine levels with SLE risk using a two-sample MR analysis. We successfully extracted three pyroglutamine-associated genetic IVs. Three IVs demonstrated no significant pleiotropy or heterogeneity in SLE GWAS. A two-sample MR analysis showed that as pyroglutamine genetically increased, the risk of SLE also increased using weighted median (OR = 3.994, 95% CI: [1.332 ∽ 11.970], p = 0.013) and Inverse Variance Weighted (IVW) (OR = 4.013, 95% CI: [1.484 ∽ 10.848], p = 0.006). Our analysis suggests a potential causal association of genetically increased pyroglutamine levels with increased SLE risk. Thus, pyroglutamine may be a potential risk factor for SLE.
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