A genetic risk score using human chromosomal-scale length variation can predict schizophrenia

Abstract

Abstract Studies indicate that schizophrenia has a genetic component, however it cannot be isolated to a single gene. We aimed to determine how well one could predict that a person will develop schizophrenia based on their germ line genetics. We compared 1129 people from the UK Biobank dataset who had a diagnosis of schizophrenia to an equal number of age matched people drawn from the general UK Biobank population. For each person, we constructed a profile consisting of numbers. Each number characterized the length of segments of chromosomes. We tested several machine learning algorithms to determine which was most effective in predicting schizophrenia and if any improvement in prediction occurs by breaking the chromosomes into smaller chunks. We found that the stacked ensemble, performed best with an area under the receiver operating characteristic curve (AUC) of 0.545 (95% CI 0.539–0.550). We noted an increase in the AUC by breaking the chromosomes into smaller chunks for analysis. Using SHAP values, we identified the X chromosome as the most important contributor to the predictive model. We conclude that germ line chromosomal scale length variation data could provide an effective genetic risk score for schizophrenia which performs better than chance.