Novel genetic loci affecting facial shape variation in humans

Xiong, Z.; Dankova, G.; Howe, L. H.; Lee, M.; Hysi, P.; de Jong, M.; Zhu, G.; Adhikari, K.; Li, D.; Li, Y.; Pan, B.; Feingold, E.; Marazita, M.; Shaffer, J.; McAloney, K.; Xu, S.; Jin, L.; Wang, S.; Vrij, F.; Lendemeijer, B.; Richmond, S.; Zhurov, A.; Lewis, S.; Sharp, G.; Paternoster, L.; Thompson, H.; Gonzales-Jose, R.; Bortolini, M. C.; Canizales-Quinteros, S.; Gallo, C.; Poletti, G.; Bedoya, G.; Rothhammer, F.; Uitterlinden, A.; Ikram, M. A.; Wolvius, E.; Kushner, S.; Nijsten, T.; Palstra, R.-J.; Boehringer, S.; Medland, S.; Tang, K.; Ruiz-Linares, A.; Martin, N.; Spector, T.; Stergiakouli

doi:10.1101/693002

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bioRxiv · 10.1101/693002

Novel genetic loci affecting facial shape variation in humans

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Abstract

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited despite the relevance for various fields of science and application. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching genome-wide significant association, among which 17 were previously unreported. A multi-ethnic study in additional 7,917 individuals confirmed 13 loci including 8 unreported ones. A global map of polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

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Xiong, Z., Dankova, G., Howe, L. H., Lee, M., Hysi, P., de Jong, M., Zhu, G., Adhikari, K., Li, D., Li, Y., Pan, B., Feingold, E., Marazita, M., Shaffer, J., McAloney, K., Xu, S., Jin, L., Wang, S., Vrij, F., Lendemeijer, B., Richmond, S., Zhurov, A., Lewis, S., Sharp, G., Paternoster, L., Thompson, H., Gonzales-Jose, R., Bortolini, M. C., Canizales-Quinteros, S., Gallo, C., Poletti, G., Bedoya, G., Rothhammer, F., Uitterlinden, A., Ikram, M. A., Wolvius, E., Kushner, S., Nijsten, T., Palstra, R.-J., Boehringer, S., Medland, S., Tang, K., Ruiz-Linares, A., Martin, N., Spector, T., Stergiakouli. 2019-07-04. Novel genetic loci affecting facial shape variation in humans. https://doi.org/10.1101/693002

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