The 88th Annual Meeting of the American Association of Physical Anthropologists (2019)


Meta-analysis identifies 48 SNPs with multiple independent effects on human facial features

JULIE D. WHITE1, JASMIEN ROOSENBOOM2, KARLIJNE INDENCLEEF3,4, JAAVED MOHAMMED5, JIARUI LI3,4, ALEJANDRA ORTEGA-CASTRILLON3,4, TOMEK SWIGUT5, MYOUNG KEUN LEE2, TOMAS GONZALEZ-ZARZAR1, ARSLAN A. ZAIDI6, JOHN R. SHAFFER7, ELEANOR FEINGOLD7,8, STEPHEN RICHMOND9, RYAN J. ELLER10, SUSAN WALSH10, MARY L. MARAZITA2,8, JOANNA WYSOCKA11,5, SETH M. WEINBERG12,2,7, PETER CLAES3,4 and MARK D. SHRIVER1.

1Department of Anthropology, Pennsylvania State University, 2Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, 3Department of Electrical Engineering, ESAT/PSI, KU Leuven, 4Medical Imaging Research Center, MIRC, UZ Leuven, 5Department of Chemical and Systems Biology, Stanford University School of Medicine, 6Department of Biology, Pennsylvania State University, 7Department of Human Genetics, University of Pittsburgh, 8Department of Biostatistics, University of Pittsburgh, 9Dental Health and Biological Sciences, College of Medicine, University of Wales, 10Department of Biology, Indiana University-Purdue University Indianapolis, 11Department of Developmental Biology, Stanford University School of Medicine, 12Department of Anthropology, University of Pittsburgh

March 28, 2019 3:45, CC Room 26 C Add to calendar

The genetic factors that have shaped contemporary facial features are unknown and likely complex. As with all complex traits, it is probable that the genetic mechanisms involved have both singular and concerted effects. We performed a meta-analysis GWAS with the imputed genetic data and 3D facial photographs of two large cohorts of European ancestry (NUS = 4,066; NUK = 3,566). We identified 213 genomic regions significantly associated with facial shape with symmetric effects in the US and UK datasets. Of these regions, 48 significantly affect multiple parts of the face (e.g. both the forehead and chin), suggesting that some of the SNPs identified have pleiotropic impacts on facial phenotypes. Gene Ontology of the 161 genes within 500 kb of these SNPs highlights functions in embryo development, skeletal development, and morphogenesis. 36 (22.36%) of the nearby genes are also transcription factors, including PAX3 and TBX15. In comparison, the 165 SNPs without multiple facial effects are collectively within 500 kb of 835 genes, of which 100 (11.97%) are identified as being transcription factors. A comparison of these two proportions has a z-score of 3.5 and a p-value of 0.0002, supporting the hypothesis of an enrichment in the association of transcription factors with pleiotropic facial SNPs compared to single-effect SNPs. This work assists us in understanding the complex effects of single SNPs on different parts of the face, an essential step forward in understanding the evolutionary processes and current genetic mechanisms regulating human facial variation.