The Relationship Between Frailty and Schizophrenia: A Genetic Association and Mendelian Randomization Study

Abstract

Abstract Importance Frailty was associated with elevated risks of various diseases and could induce many adverse outcomes in schizophrenia patients. However, the association and causality between frailty and schizophrenia are still unclear.Objective To investigate the genetic association and causality between frailty and schizophrenia.Design, Setting, and Participants We obtained the summary genetic data related to frailty and schizophrenia from the large-scale genome-wide association studies in the European population. Genetic association analyses were investigated from 5 aspects: global genetic correlation, local genetic correlation, shared genomic loci, overlapped tissue enrichments, and shared functional genes. The causality was inferred via the bidirectional Mendelian Randomization (MR) analyses.Main Outcomes and Measures The genetic association and causality between frailty and schizophrenia.Results The global genetic correlation analyses presented they were positively associated, and the local genetic correlation analyses demonstrated they were locally correlated in three genomes. Furthermore, 111 genomic loci were found to be jointly associated with frailty and schizophrenia. Additionally, the tissue enrichment and summary-data-based MR analyses demonstrated the genetic variants related to frailty and schizophrenia have overlapped tissue enrichments and functional genes in the brain. Lastly, the MR results implied there was a bidirectional causal relationship between frailty and schizophrenia.Conclusions and Relevance Our study indicated that frailty and schizophrenia had plenty of shared genetic basis and supported their bidirectional causality. Further studies are warranted to validate these findings in non-European populations.