AUTHOR=Wang Peiqi , Sun Xinghan , Miao Qiang , Mi Hao , Cao Minyuan , Zhao Shan , Wang Yiyi , Shu Yang , Li Wei , Xu Heng , Bai Ding , Zhang Yan 

TITLE=Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.967684

DOI=10.3389/fgene.2022.967684

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> In total, 21 genetic associations were identified, of which ten were novel: <italic>GMDS-AS1</italic> (rs4959669, <italic>p</italic> = 1.29 × 10<sup>−49</sup>) and <italic>SPRED2</italic> (rs13423753, <italic>p</italic> = 2.99 × 10<sup>−14</sup>) for widow’s peak, a previously unreported trait; <italic>FARSB</italic> (rs36015125, <italic>p</italic> = 1.96 × 10<sup>−21</sup>) for unibrow; <italic>KIF26B</italic> (rs7549180, <italic>p</italic> = 2.41 × 10<sup>−15</sup>), <italic>CASC2</italic> (rs79852633, <italic>p</italic> = 4.78 × 10<sup>−11)</sup>, <italic>RPGRIP1L</italic> (rs6499632, <italic>p</italic> = 9.15 × 10<sup>−11</sup>), and <italic>PAX1</italic> (rs147581439, <italic>p</italic> = 3.07 × 10<sup>−8</sup>) for double eyelid; <italic>ZFHX3</italic> (rs74030209, <italic>p</italic> = 9.77 × 10<sup>−14</sup>) and <italic>LINC01107</italic> (rs10211400, <italic>p</italic> = 6.25 × 10<sup>−10</sup>) for earlobe attachment; and <italic>SPATA33</italic> (rs35415928, <italic>p</italic> = 1.08 × 10<sup>−8</sup>) 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.</p><p><bold>Conclusion:</bold> 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.</p>