To construct subtype-specific PRSs, we evaluated four different methods: (1) using effect sizes for overall breast cancer (for each of the subtypes), (2) using effect sizes for subtype-specific (ER-positive or ER-negative) disease, (3) using a hybrid method, in which effect sizes were estimated in the relevant subtype for SNPs passing a certain optimal significance threshold in a case-only logistic regression (ER-positive versus ER-negative disease), and otherwise, using effect sizes estimated for overall breast cancer, or (4) by estimating case-only ORs using lasso and combining these with the overall breast cancer ORs to derive subtype-specific estimates, using the formulae:βERpositive=βoverall+η∗βcase-onlyβERnegative=βoverall-(1-η)∗βcase-onlywhere η = 0.27 was the proportion of ER-negative tumors in the validation set.