Using results from >400,000 participants in two-sample Mendelian randomization, we show that genetically raised LDL-cholesterol is associated with higher risk of breast cancer (odds ratio, OR, per standard deviation, 1.09, 95% confidence interval, 1.02–1.18, P = 0.020) and estrogen receptor (ER)-positive breast cancer (OR 1.14 [1.05–1.24] P = 0.004). Here, ESR1 is linked to breast cancer.