<p>Assessment Causality in Associations Between Serum Uric Acid and Risk of Schizophrenia: A Two-Sample Bidirectional Mendelian Randomization Study</p>

Abstract

Although increasing lines of evidence showed associations between serum uric acid (UA) levels and schizophrenia, the causality and the direction of the associations remain uncertain. Thus, we aimed to assess whether the relationships between serum UA levels and schizophrenia are causal and to determine the direction of the association. Patients and Methods: Two-sample bidirectional Mendelian randomization (MR) analyses and various sensitivity analyses were performed utilizing the summary data from genome-wide association studies within the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium. Secondary MR analyses in both directions were conducted within summary data using genetic risk scores (GRSs) as instrumental variables. Results: Three MR methods provided no causal relationship between serum UA and schizophrenia. Furthermore, GRS approach showed similar results in the three MR methods after adjustment for heterogeneity. By contrast, inverse variance weighted method, weighted median and GRS approach suggested a causal effect of schizophrenia risk on serum UA after adjustment for heterogeneity (per 10-symmetric percentage increase in schizophrenia risk, beta: −0.039, standard error (SE): 0.013, P = 0.003; beta: −0.036, SE: 0.018, P = 0.043; beta: −0.039, SE: 0.013, P = 0.002; respectively). Moreover, in both directions' analyses, the heterogeneity and sensitivity tests suggested no strong evidence of bias due to pleiotropy. Conclusion: Schizophrenia may causally affect serum UA levels, whereas the causal role of serum UA concentrations in schizophrenia was not supported by our MR analyses. These findings suggest that UA may be a useful potential biomarker for monitoring treatment or diagnosis of schizophrenia rather than a therapeutic target for schizophrenia.

Childhood maltreatment increases the suicidal risk in Chinese schizophrenia patients

“…Schizophrenia (SCZ) is a complex dysfunction of genetic, heterogeneous behavioral and cognitive syndrome that is prevalent in ~1% of the general population around the world, whose origins etiology appear to lie in genetic and/or environmental disruption of brain development ( 1 ). Life expectancy for people with SCZ is probably 10–25 years shorter than that for the general people ( 2 , 3 ).…”

Role of uric acid as a biomarker of cognitive function in schizophrenia during maintenance period

“…However, the relationship between UA and cognitive impairment in patients with SCZ in maintenance period, an important period, remains largely unexplored. A genome-wide association study suggested that low UA may be associated with SCZ pathogenesis and is more suitable for diagnostic and therapeutic testing than other markers ( 54 ). The findings of the present study suggested that high serum UA may serve as a potential blood biomarker for the assessment of cognitive improvement in SCZ.…”

Uric Acid Potential Role in Systemic Inflammation and Negative Symptoms After Acute Antipsychotic Treatment in Schizophrenia

“…To date, it is still not clear whether serum UA levels should be considered in schizophrenia onset or as an outcome of disease progression. Complex analyses of the data from genome-wide association studies within the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium revealed no causal role of serum UA concentrations in schizophrenia, suggesting that low UA levels may be a consequence of schizophrenia onset and are more appropriate for diagnostic purposes or treatment monitoring ( 27 ). We examined serum UA levels in different phases of schizophrenia and found no significant difference between FEP and SC in relapse patients, nor 1 month after applied therapy in FEP.…”