Genome-wide Association Study of Estradiol Levels and the Causal Effect of Estradiol on Bone Mineral Density

Estradiol is the primary female sex hormone and plays an important role for skeletal health in both sexes. Several enzymes are involved in estradiol metabolism, but few genome-wide association studies (GWAS) have been performed to characterize the genetic contribution to variation in estrogen levels. Identify genetic loci affecting estradiol levels and estimate causal effect of estradiol on bone mineral density (BMD). We performed GWAS for estradiol in males (n = 147 690) and females (n = 163 985) from UK Biobank. Estradiol was analyzed as a binary phenotype above/below detection limit (175 pmol/L). We further estimated the causal effect of estradiol on BMD using Mendelian randomization. We identified 14 independent loci associated (P