Analysis of sex-differential gene expression on the target of approved drug

Abstract

Abstract Sex is a key piece of patient information but is often not actively considered in drug use. This is partly due to the lack of molecular evidence at the gene expression level beyond sex chromosomes and sex hormones. We aim to investigate how sex differences in tissue-specific gene expression relate to FDA-approved drugs using the latest database of The Genotype-Tissue Expression (GTEx) V10. Our analysis reveals that 91.4% of FDA-approved drug target genes exhibit sex-differential expression in at least one tissue. The tissues with the most pronounced sex differences include subcutaneous adipose tissue, skeletal muscle, and the pituitary gland, while sex differences are less pronounced in the liver, other brain regions, and the spleen. Sex-differential disease-related genes include those associated with obesity (PPARG, INSR), cancer (FGFR1, CD22), and immunity (IL6R, IL3RA). Based on our findings, we advocate for a policy shift that integrates sex-based molecular data into preclinical studies, drug development, and clinical practices. This paradigm aligns biomedical research with precision medicine, mitigates drug-related risks, and promotes equitable healthcare outcomes.