Asparagine reduces the risk of schizophrenia: a bidirectional two-sample mendelian randomization study of aspartate, asparagine and schizophrenia

Abstract

Background Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. Methods This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. Results No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483–3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987–1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999–1.011, P-value = 0.132). Conclusion This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study

“…Mendelian randomization of selected instrumental variables for genetic variation must be based on three fundamental assumptions: the correlation hypothesis, which postulates a strong correlation between SNPs and exposure factors; the independence hypothesis, which asserts that SNPs are not affected by various confounders; and the exclusivity hypothesis, which argues that SNPs affect the outcome only through exposure factors 25 , 26 . In our study, IVs for each immune phenotype were identified with a stringent significance threshold of 5e-8, employing PLINK (v1.90) for SNP trimming based on linkage disequilibrium (LD; r2 < 0.001 within a 10,000 kb radius).…”