title: Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.
abstract: Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10-8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.
authors: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: John R
authors: JR
authors: Shaffer
authors: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Ekaterina
authors: http://orcid.org/0000-0002-7129-5796
authors: E
authors: Orlova
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Myoung Keun
authors: MK
authors: Lee
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Elizabeth J
authors: http://orcid.org/0000-0002-5735-1712
authors: EJ
authors: Leslie
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Zachary D
authors: ZD
authors: Raffensperger
authors: Department of Pediatrics, Seattle Children's Craniofacial Center, University of Washington, Seattle, Washington, United States of America.
authors: Carrie L
authors: CL
authors: Heike
authors: Department of Pediatrics, Seattle Children's Craniofacial Center, University of Washington, Seattle, Washington, United States of America.
authors: Michael L
authors: ML
authors: Cunningham
authors: Department of Pediatrics, University of Texas McGovern Medical Center, Houston, Texas, United States of America.
authors: Jacqueline T
authors: JT
authors: Hecht
authors: Department of Orthodontics, University of Alabama, Birmingham, Alabama, United States of America.
authors: Chung How
authors: CH
authors: Kau
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America.
authors: Nichole L
authors: http://orcid.org/0000-0001-6458-9991
authors: NL
authors: Nidey
authors: Department of Orthodontics, University of Iowa, Iowa City, Iowa, United States of America.|Dows Institute, University of Iowa, Iowa City, Iowa, United States of America.
authors: Lina M
authors: LM
authors: Moreno
authors: Department of Health Management and Policy, University of Iowa, Iowa City, Iowa, United States of America.
authors: George L
authors: GL
authors: Wehby
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America.
authors: Jeffrey C
authors: JC
authors: Murray
authors: Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
authors: Cecelia A
authors: CA
authors: Laurie
authors: Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
authors: Cathy C
authors: CC
authors: Laurie
authors: Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors: Joanne
authors: http://orcid.org/0000-0001-9520-2788
authors: J
authors: Cole
authors: Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors: Tracey
authors: http://orcid.org/0000-0003-2698-1022
authors: T
authors: Ferrara
authors: Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, United States of America.|Department of Mathematical and Statistical Sciences, University of Colorado, Denver, Denver, Colorado, United States of America.
authors: Stephanie
authors: S
authors: Santorico
authors: Department of Orofacial Sciences, University of California, San Francisco, San Francisco, California, United States of America.|Department of Pediatrics, University of California, San Francisco, San Francisco, California, United States of America.|Program in Craniofacial Biology, University of California, San Francisco, California, United States of America.
authors: Ophir
authors: O
authors: Klein
authors: Department of Mathematics, Florida State University, Tallahassee, Florida, United States of America.
authors: Washington
authors: http://orcid.org/0000-0003-1106-8089
authors: W
authors: Mio
authors: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Eleanor
authors: E
authors: Feingold
authors: Department of Cell Biology & Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Benedikt
authors: B
authors: Hallgrimsson
authors: Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, United States of America.|Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors: Richard A
authors: RA
authors: Spritz
authors: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Mary L
authors: ML
authors: Marazita
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Anthropology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Seth M
authors: SM
authors: Weinberg
mesh_terms: D005145:Face / Q000033:anatomy & histology*; D056726:Genetic Association Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008445:Maxillofacial Development / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics; D044465:White People
chemical_list: D014157:Transcription Factors