Schizophrenia and risk preference: a bidirectional two-sample mendelian randomization study

Increasing evidence shows that risk preference is associated with schizophrenia. However, the causality and direction of this association are not clear; Therefore, we used Mendelian randomization (MR) to examine the potential bidirectional relationship between risk preference and schizophrenia. Genome-wide association studies (GWAS) summary data on risk preference of 939,908 participants from the UK Biobank and 23andMe were used to identify general risk preference. Data from 320,404 subjects (76,755 cases and 243,649 controls) from The Psychiatric Genomics Consortium were used to identify schizophrenia. The weighted median (WM), the inverse variance weighted (IVW), and the Mendelian randomization-Egger (MR-Egger) methods were used for the MR analysis to estimate the causal effect and detect the directional pleiotropy. The GWAS summary data were respectively from two combined samples, containing 939,908 and 320,404 subjects of European ancestry. Mendelian randomization evidence suggested that risk preference was associated with increased onset of schizophrenia (OR = 2.84, 95CI%: 1.77-4.56, P = 1.58*10 - 5) and that schizophrenia was also associated with raised risk preference (OR = 1.11, 95CI%: 1.07-1.15, P = 7.98*10 - 8). With the use of large-scale GWAS data, robust evidence suggests an interaction between risk preference and schizophrenia. This also indicates that early identification of and intervention for increased risk preference may improve the prognosis of schizophrenia.