The relationship between schizophrenia polygenic scores, blood-based proteins and psychosis diagnosis in the UK Biobank

Despite notable progress in psychiatric genomics, there are no validated blood-based biomarkers for psychosis. Previous studies have failed to establish a link between schizophrenia polygenic scores (PGS) and blood protein levels. We aimed to identify associations between schizophrenia PGS and blood-based proteins, and to determine whether levels of these proteins differ in individuals with psychosis. We analysed proteomic and genomic data from 49,083 participants in the UK Biobank. Association analyses, excluding individuals with psychosis, identified nominal associations (p < 0.05) of schizophrenia PGS with 109 proteins. Four of these (TMPRSS15, ADGRB3, CEACAM21, and KLK1) met the false discovery rate (FDR) threshold of < 0.05. We investigated the association of these four proteins with psychosis in a matched case-control sample (291 cases, 873 controls). In individuals with psychosis, we observed significantly higher levels of TMPRSS15 (effect size 0.22, standard error 0.07, FDR 6.97 × 10 ⁻³ ) and lower levels of KLK1 (effect size −0.23, SE 0.09, FDR 3.34 × 10 ⁻² ). These two proteins should be taken forward for further study and validation aimed at investigating their potential as psychosis biomarkers.