Moreover, the SNP has not been associated with testosterone levels, making it suitable to estimate the independent effect of estradiol.13 Also, the SNP has been validated against known or suspected estradiol-related traits, such as bone mineral density and insulin sensitivity, as well as estrogen receptor positive breast cancer and endometrial cancer.13,29 Finally, MR estimates lifetime effects rather than acute effects. Here, INS is linked to breast carcinoma.