Cross-trait genetic architecture between breast cancer and psychiatric disorders

Abstract

Summary Breast cancer (BC) and psychiatric disorders are epidemiologically linked, raising the possibility of shared genetic influences. Based on the summary statistics from the genome-wide association studies (GWAS), the genetic correlation and overlap between psychiatric disorders and BC were investigated. Shared pleiotropic loci and genes were identified via cross-trait analyses. Functional annotations and tissue-specific enrichment were carried out to determine potential associations. A total of 7,274 pleiotropic single nucleotide polymorphisms (SNPs) were identified by cross-trait analyses. Furthermore, 156 shared genomic risk loci were identified by annotation, of which 19 passed the colocalization test. The gene-level analysis discovered 142 pleiotropic genes, among which MRTFA and FGFR2 were identified in most trait pairs. Pathway enrichment highlighted positive regulation of RNA. Finally, protein quantitative trait locus (pQTL)-based summary-data-based Mendelian randomization (SMR) analyses further prioritized plasma proteins associated with both phenotypes. These findings delineate a common genetic basis for BC and psychiatric conditions, offering insights into their comorbidity.