Genotype-driven variations in lncRNA expression underlie predisposition to high-grade serous ovarian cancer

New effective early diagnosis strategies and therapeutic targets are desperately needed for high-grade serous ovarian cancer (HGSOC). Previous functional interpretation of HGSOC genome-wide association studies (GWAS) largely neglected long non-coding RNAs (lncRNAs). Here, we map genotype effects on the expression of both protein-coding genes (PCGs) and lncRNAs in 348 HGSOC tumor samples. We show that underlying genetic variants are significant drivers of expression changes for both PCGs and lncRNAs. Importantly, lncRNAs account for a higher portion of HGSOC heritability than PCGs. Bayesian colocalization analysis prioritized causal genes in HGSOC tumors and whole blood, such as ARL17A and CRHR1-IT1 . Using single-nucleus transcriptome maps of HGSOC tumors generated by snRandom-seq, we characterized expression patterns of candidate susceptibility genes. Furthermore, we validated the role of CRHR1-IT1 in promoting apoptosis and inhibiting the growth of HGSOC cells. Our study provides new insights into early detection and immunotherapy development for HGSOC.