The optimum subtype-specific PRS was obtained when a subset of these 313 SNPs (196 SNPs with a case-only p value for association with ER-negative versus ER-positive disease of p < 0.025) were given subtype-specific weights, while the remaining SNPs were given overall breast cancer weights. For ER-negative disease, the OR improved from OR = 1.45 (95%CI: 1.35–1.56) to OR = 1.47 (95%CI: 1.37–1.58) using the hybrid method compared with using only subtype-specific estimates, while for ER-positive disease the results were similar (OR = 1.74) (Tables S6 and S7).