097 Evidence of a female-specific causal relationship between endogenous testosterone levels and acne

To investigate a potential causal role of natural variation in endogenous testosterone levels the development acne, we performed two-sample sex-stratified Mendelian randomisation (MR) study. Instrumental variables comprised genetic variants with genome-wide significant effects on total (TT), free (FT) and steroid hormone binding globulin (SHBG) male female participants UK Biobank. The these instrumental acne were derived from association studies comprising 3,173 cases 2,426 cases. Inverse-variance weighted MR estimates did not support for traits risk males (ORTT = 1.00 (0.85-1.18), pTT 0.98; ORFT 1.02 (0.79-1.31), pFT 0.87; ORSHBG 0.91 (0.70-1.18), pSHBG 0.47). In females, associated increased conferred proportional increase 1.79 (1.38-2.32), 1.0x10-5; 2.30 (1.53-3.45), 5.8x10-5). Whereas SHBG decrease (ORSHBG 0.68 (0.50-0.93), 0.016). Dissection variable sets indicated that effect females is driven by specific to testosterone, independent (OR 2.29 (1.46-3.58), p 2.8x10-4). Our data are consistent endogenous, SHBG-independent, contributing casual biological pathways acne. discordant suggestive pathophysiological sexual dimorphism severe motivates further investigations.