Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing.

ABSTRACT: Major depressive disorder (MDD) is the single largest contributor to global disability and up to 20-30% of patients do not respond to at least two antidepressants (treatment-resistant depression, TRD). This study leveraged imputed gene expression in TRD to perform a drug repurposing analysis. Among those with MDD, we defined TRD as having at least two antidepressant switches according to primary care records in UK Biobank (UKB). We performed a transcriptome-wide association study (TWAS) of TRD (n = 2165) vs healthy controls (n = 11,188) using FUSION and gene expression levels from 21 tissues. We identified compounds with opposite gene expression signatures (ConnectivityMap data) compared to our TWAS results using the Kolmogorov-Smirnov test, Spearman and Pearson correlation. As symptom pat

SUBMITTER: Fabbri C 

PROVIDER: S-EPMC8357803 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature