rs12150660

rs12150660 is a common intronic variant in the SHBG gene at 17p13.1 and the lead signal in the largest genome-wide meta-analysis of circulating sex hormone-binding globulin (Coviello et al., PLoS Genetics 2012; 21,791 discovery plus 7,046 follow-up individuals, p = 1.8e-106). It does not change the SHBG protein; instead it sits in near-complete linkage (r-squared above 0.95) with a (TAAAA)n pentanucleotide repeat in the SHBG promoter that alters how much SHBG the liver transcribes, so the T allele tracks higher circulating SHBG — about 11% more per copy, or roughly 23% comparing T/T to G/G. UK Biobank's own deposited summary statistics put the per-allele effect at 0.116 standard deviations in 180,726 men and 0.097 in 188,000 women, so the lean is modestly stronger in men, not dramatically so: comparing the two homozygote groups shifts the odds of sitting in the bottom fifth of the SHBG distribution by about 1.4-fold in men and 1.3-fold in women. Because SHBG binds and limits the free, bioavailable fraction of testosterone and estradiol, it underlies the Sex-hormone transport trait. Two important limits: the effect has only ever been estimated in European-ancestry cohorts, and the T allele is essentially absent from East Asian populations (gnomAD East Asian frequency 0.19%), so the variant carries little information there.