Bioinformatics Seminar
Time: 11AM
Venue: Davis Auditorium and Online
31 March 2026
Genetics-led discovery of cognitive deficits in Schizophrenia
Khanh VuWEHI
Cognitive impairment is a core feature of schizophrenia (SCZ), spanning deficits in processing speed, executive function, and memory. However, because these cognitive domains are highly intercorrelated, and vary significantly between patients, identifying the specific biological drivers of these deficits remains a challenge. Consequently, cognitive deficits in SCZ remain inadequately treated by existing pharmacotherapies. In this project, we leverage genetics data from genome wide association studies (GWAS) to uncover the biological mechanisms behind cognitive deficits in SCZ. Using GWAS data from the UK Biobank, we constructed a network of conditional genetic correlations across cognitive tests reflecting processing speed, executive function, working memory, reasoning, and visual memory. This refined which cognitive domains still display evidence of genetic overlap after accounting for all other cognitive traits tested. Integration of schizophrenia into the cognitive genetic network demonstrated that a measure of executive function, indexed by the trail making test (TM2), is the cognitive domain with the strongest genetic link to schizophrenia after conditioning on all other features. We further examined this relationship using PW-GWAS, a Bayesian method to find shared loci and gene between the 2 traits. We found 16 genomic regions shared between 2 traits with posterior probabilities greater than 0.9 and 6 shared genes with posterior probabilities greater than 0.8. Using drug repurposing database, we identified 5 approved epilepsy drugs to be potential candidates for treating cognitive deficits in SCZ. These results highlight a shared genetic architecture between schizophrenia and executive function, identifying 5 approved epilepsy medications as potential candidates for repurposing to treat cognitive impairment in SCZ.