Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.
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 d...
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Public Library of Science (PLoS)
2016-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006149&type=printable |
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| author | John R Shaffer Ekaterina Orlova Myoung Keun Lee Elizabeth J Leslie Zachary D Raffensperger Carrie L Heike Michael L Cunningham Jacqueline T Hecht Chung How Kau Nichole L Nidey Lina M Moreno George L Wehby Jeffrey C Murray Cecelia A Laurie Cathy C Laurie Joanne Cole Tracey Ferrara Tracey Ferrara Stephanie Santorico Ophir Klein Washington Mio Eleanor Feingold Benedikt Hallgrimsson Richard A Spritz Mary L Marazita Seth M Weinberg |
| author_facet | John R Shaffer Ekaterina Orlova Myoung Keun Lee Elizabeth J Leslie Zachary D Raffensperger Carrie L Heike Michael L Cunningham Jacqueline T Hecht Chung How Kau Nichole L Nidey Lina M Moreno George L Wehby Jeffrey C Murray Cecelia A Laurie Cathy C Laurie Joanne Cole Tracey Ferrara Tracey Ferrara Stephanie Santorico Ophir Klein Washington Mio Eleanor Feingold Benedikt Hallgrimsson Richard A Spritz Mary L Marazita Seth M Weinberg |
| author_sort | John R Shaffer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ed7692180bbb452eb4bebb2f863ab148 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-08-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-ed7692180bbb452eb4bebb2f863ab1482025-08-20T02:40:27ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-08-01128e100614910.1371/journal.pgen.1006149Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.John R ShafferEkaterina OrlovaMyoung Keun LeeElizabeth J LeslieZachary D RaffenspergerCarrie L HeikeMichael L CunninghamJacqueline T HechtChung How KauNichole L NideyLina M MorenoGeorge L WehbyJeffrey C MurrayCecelia A LaurieCathy C LaurieJoanne ColeTracey FerraraTracey FerraraStephanie SantoricoOphir KleinWashington MioEleanor FeingoldBenedikt HallgrimssonRichard A SpritzMary L MarazitaSeth M WeinbergNumerous 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006149&type=printable |
| spellingShingle | John R Shaffer Ekaterina Orlova Myoung Keun Lee Elizabeth J Leslie Zachary D Raffensperger Carrie L Heike Michael L Cunningham Jacqueline T Hecht Chung How Kau Nichole L Nidey Lina M Moreno George L Wehby Jeffrey C Murray Cecelia A Laurie Cathy C Laurie Joanne Cole Tracey Ferrara Tracey Ferrara Stephanie Santorico Ophir Klein Washington Mio Eleanor Feingold Benedikt Hallgrimsson Richard A Spritz Mary L Marazita Seth M Weinberg Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. PLoS Genetics |
| title | Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. |
| title_full | Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. |
| title_fullStr | Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. |
| title_full_unstemmed | Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. |
| title_short | Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. |
| title_sort | genome wide association study reveals multiple loci influencing normal human facial morphology |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006149&type=printable |
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