The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics.

Department of Anatomy and Cell Biology and McCaig Institute for Bone and Joint Health University of Calgary Calgary Canada

Department of Anatomy Catholic University of Health and Allied Sciences Mwanza Tanzania

Department of Biochemistry and Molecular Genetics University of Colorado School of Medicine Aurora Colorado United States of America

Department of Biostatistics and Informatics Colorado School of Public Health Aurora Colorado United States of America

Department of Craniofacial Biology University of Colorado School of Dental Medicine Aurora Colorado United States of America

Department of Mathematical and Statistical Science University of Colorado Denver Denver Colorado United States of America

Department of Mathematics Florida State University Tallahassee Florida United States of America

Department of Orofacial Sciences and Program in Craniofacial Biology University of California San Francisco San Francisco California United States of America

Department of Pediatrics University of Colorado School of Medicine Aurora Colorado United States of America

Hotchkiss Brain Institute Cummings School of Medicine University of Calgary Calgary Canada

Human Medical Genetics and Genomics Program University of Colorado School of Medicine Aurora Colorado United States of America

Laboratory of Transgenic Models of Diseases Institute of Molecular Genetics of the ASCR Prague Czech Republic

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PLoS Genet. 2016 Aug 25;12(8):e1006250. doi: 10.1371/journal.pgen.1006250. PubMed

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