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Many factors influence human facial morphology, including genetics, age, nutrition, biomechanical forces, and endocrine factors. Moreover, facial features clearly differ between males and females, and these differences are driven primarily by the influence of sex hormones during growth and development. Specific genetic variants are known to influence circulating sex hormone levels in humans, which we hypothesize, in turn, affect facial features. In this study, we investigated the effects of testosterone-related genetic variants on facial morphology. We tested 32 genetic variants across 22 candidate genes related to levels of testosterone, sex hormone-binding globulin (SHGB) and dehydroepiandrosterone sulfate (DHEAS) in three cohorts of healthy individuals for which 3D facial surface images were available (Pittsburgh 3DFN, Penn State and ALSPAC cohorts; total  n  = 7418). Facial shape was described using a recently developed extension of the dense-surface correspondence approach, in which the 3D facial surface was partitioned into a set of 63 hierarchically organized modules. Each variant was tested against each of the facial surface modules in a multivariate genetic association-testing framework and meta-analyzed. Additionally, the association between these candidate SNPs and five facial ratios was investigated in the Pittsburgh 3DFN cohort. Two significant associations involving intronic variants of  SHBG  were found: both rs12150660 ( p  = 1.07E-07) and rs1799941 ( p  = 6.15E-06) showed an effect on mandible shape. Rs8023580 (an intronic variant of  NR2F2-AS1 ) showed an association with the total and upper facial width to height ratios ( p  = 9.61E-04 and  p  = 7.35E-04, respectively). These results indicate that testosterone-related genetic variants affect normal-range facial morphology, and in particular, facial features known to exhibit strong sexual dimorphism in humans.

SNPs Associated With Testosterone Levels Influence Human Facial Morphology