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Most women with epithelial ovarian cancer (EOC) are diagnosed after the disease has metastasized and survival in this group remains poor. Circulating proteins associated with the risk of developing EOC have the potential to serve as biomarkers for early detection and diagnosis. We integrated large-scale genomic and proteomic data to identify novel plasma proteins associated with EOC risk. We used the germline genetic variants most strongly associated (P <1.5 × 10−11) with plasma levels of 1329 proteins in 3301 healthy individuals from the INTERVAL study to predict circulating levels of these proteins in 22,406 EOC cases and 40,941 controls from the Ovarian Cancer Association Consortium (OCAC). Association testing was performed by weighting the beta coefficients and standard errors for EOC risk from the OCAC study by the inverse of the beta coefficients from INTERVAL. We identified 26 proteins whose genetically predicted circulating levels were associated with EOC risk at false discovery rate < 0.05. The 26 proteins included MFAP2, SEMG2, DLK1, and NTNG1 and a group of 22 proteins whose plasma levels were predicted by variants at chromosome 9q34.2. All 26 protein association signals identified were driven by association with the high-grade serous histotype that comprised 58% of the EOC cases in OCAC. Regional genomic plots confirmed overlap of the genetic association signal underlying both plasma protein level and EOC risk for the 26 proteins. Pathway analysis identified enrichment of seven biological pathways among the 26 proteins (P adjusted <0.05), highlighting roles for Focal Adhesion-PI3K-Akt-mTOR and Notch signaling. The identified proteins further illuminate the etiology of EOC and represent promising new EOC biomarkers for targeted validation by studies involving direct measurement of plasma proteins in EOC patient cohorts. • This study analyzed 667 germline genetic variants known to be associated with circulating (plasma) levels of 1329 proteins • These variants were used to predict plasma protein levels in 22,406 epithelial ovarian cancer cases and 40,941 controls • Genetically predicted levels of 26 proteins were associated with all invasive epithelial ovarian cancer risk • The identified proteins were enriched for the Focal Adhesion-PI3K-Akt-mTOR signaling, Notch signaling, and other pathways • The identified proteins have the potential to serve as circulating biomarkers for epithelial ovarian cancer risk [ABSTRACT FROM AUTHOR]