Journal article
Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology
PLoS genetics, Vol.12(8), pp.e1006149-e1006149
08/2016
DOI: 10.1371/journal.pgen.1006149
PMCID: PMC4999139
PMID: 27560520
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.
Details
- Title: Subtitle
- Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology
- Creators
- John R Shaffer - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaEkaterina Orlova - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaMyoung Keun Lee - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaElizabeth J Leslie - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaZachary D Raffensperger - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaCarrie L Heike - Department of Pediatrics, Seattle Children's Craniofacial Center, University of Washington, Seattle, Washington, United States of AmericaMichael L Cunningham - Department of Pediatrics, Seattle Children's Craniofacial Center, University of Washington, Seattle, Washington, United States of AmericaJacqueline T Hecht - Department of Pediatrics, University of Texas McGovern Medical Center, Houston, Texas, United States of AmericaChung How Kau - Department of Orthodontics, University of Alabama, Birmingham, Alabama, United States of AmericaNichole L Nidey - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of AmericaLina M Moreno - Dows Institute, University of Iowa, Iowa City, Iowa, United States of AmericaGeorge L Wehby - Department of Health Management and Policy, University of Iowa, Iowa City, Iowa, United States of AmericaJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of AmericaCecelia A Laurie - Department of Biostatistics, University of Washington, Seattle, Washington, United States of AmericaCathy C Laurie - Department of Biostatistics, University of Washington, Seattle, Washington, United States of AmericaJoanne Cole - Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaTracey Ferrara - Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaStephanie Santorico - Department of Mathematical and Statistical Sciences, University of Colorado, Denver, Denver, Colorado, United States of AmericaOphir Klein - Program in Craniofacial Biology, University of California, San Francisco, California, United States of AmericaWashington Mio - Department of Mathematics, Florida State University, Tallahassee, Florida, United States of AmericaEleanor Feingold - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaBenedikt Hallgrimsson - McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaRichard A Spritz - Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaMary L Marazita - Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of AmericaSeth M Weinberg - Department of Anthropology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.12(8), pp.e1006149-e1006149
- DOI
- 10.1371/journal.pgen.1006149
- PMID
- 27560520
- PMCID
- PMC4999139
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7390
- eISSN
- 1553-7404
- Publisher
- Public Library Science; United States
- Grant note
- U01 DE020054 / NIDCR NIH HHS HHSN268201200008I / NHLBI NIH HHS R01 DE016148 / NIDCR NIH HHS R01 DE008559 / NIDCR NIH HHS U01 DE020078 / NIDCR NIH HHS K99 DE025060 / NIDCR NIH HHS U01 DE020057 / NIDCR NIH HHS HHSN268201200008C / NHLBI NIH HHS U01 DE024425 / NIDCR NIH HHS
- Language
- English
- Date published
- 08/2016
- Academic Unit
- Preventive and Community Dentistry; Orthodontics; Anatomy and Cell Biology; Health Management and Policy; Stead Family Department of Pediatrics; Epidemiology; Economics; Addiction Medicine; Pediatric Dentistry; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984025365702771
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