Abstract
Background: The aesthetic facial traits are closely related to life quality and strongly influenced by genetic factors, but the genetic predispositions in the Chinese population remain poorly understood. Methods: A genome-wide association studies (GWAS) and subsequent validations were performed in 26,806 Chinese on five facial traits: widow's peak, unibrow, double eyelid, earlobe attachment, and freckles. Functional annotation was performed based on the expression quantitative trait loci (eQTL) variants, genome-wide polygenic scores (GPSs) were developed to represent the combined polygenic effects, and single nucleotide polymorphism (SNP) heritability was presented to evaluate the contributions of the variants. Results: In total, 21 genetic associations were identified, of which ten were novel: GMDS-AS1 (rs4959669, p = 1.29 × 10(-49)) and SPRED2 (rs13423753, p = 2.99 × 10(-14)) for widow's peak, a previously unreported trait; FARSB (rs36015125, p = 1.96 × 10(-21)) for unibrow; KIF26B (rs7549180, p = 2.41 × 10(-15)), CASC2 (rs79852633, p = 4.78 × 10(-11)), RPGRIP1L (rs6499632, p = 9.15 × 10(-11)), and PAX1 (rs147581439, p = 3.07 × 10(-8)) for double eyelid; ZFHX3 (rs74030209, p = 9.77 × 10(-14)) and LINC01107 (rs10211400, p = 6.25 × 10(-10)) for earlobe attachment; and SPATA33 (rs35415928, p = 1.08 × 10(-8)) for freckles. Functionally, seven identified SNPs tag the missense variants and six may function as eQTLs. The combined polygenic effect of the associations was represented by GPSs and contributions of the variants were evaluated using SNP heritability. Conclusion: These identifications may facilitate a better understanding of the genetic basis of features in the Chinese population and hopefully inspire further genetic research on facial development.