Testosterone-related Genetic Variants are Associated With Human Facial Morphology

Objectives: Many factors influence human facial morphology; these include genetic variants, age, nutrition, biomechanical forces, and endocrine factors. Facial features clearly differ between males and females, 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. Such variants are excellent candidates for facial genetic studies, particularly for traits that show strong sexual dimorphism. In this study, we investigated the effects of testosterone-related genetic variants on facial morphology.
Methods: A literature-based list of 44 genetic variants in 22 genes related to testosterone, sex hormone-binding globulin (SHGB) and dehydroepiandrosterone sulfate (DHEAS) levels in humans was compiled and tested in a dataset of 2329 healthy individuals for which 3D facial surface images were available. Facial shape was quantified from the 3D images using a recently developed extension of the dense-surface correspondence approach, in which the 3D facial surface is partitioned into a set of 63 hierarchically organized modules. Each genetic variant was tested against each facial surface module in a multivariate genetic association-testing framework. This approach allowed identification of genetic variants that have highly localized effects on facial shape.
Results: We found nominal associations (p<0.05) between 29 of the 44 testosterone-related genetic variants and distinct aspects of facial morphology. Six variants surpassed the adjusted significance threshold of p=0.001. Of note, two variants in SHBG were associated with modules describing mandibular shape (rs12150660, p=5.50E-5; rs1799941, p=3.91E-5). Two variants in JMJD1C were associated with modules describing both nose and forehead shape (rs10822184, p=5.40E-4; rs7910927, p=1.03E-4).
Conclusions: The facial regions most strongly associated with testosterone-related genetic variants - the mandible, nose, and forehead - are also known to differ in shape between males and females. These findings may help explain certain between- and within-sex differences in facial morphology.