1. New entries in the lottery of facial GWAS discovery
- Author
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Shaffer, John R., Orlova, Ekaterina, Lee, Myoung Keun, Leslie, Elizabeth J., Raffensperger, Zachary D., Heike, Carrie L., Cunningham, Michael L., Hecht, Jacqueline T., Kau, Chung How, Nidey, Nichole L., Moreno, Lina M., Wehby, George L., Murray, Jeffrey C., Laurie, Cecelia A., Laurie, Cathy C., Cole, Joanne, Ferrara, Tracey, Santorico, Stephanie, Klein, Ophir, Mio, Washington, Feingold, Eleanor, Hallgrimsson, Benedikt, Spritz, Richard A., Marazita, Mary L., and Weinberg, Seth M.
- Subjects
Heredity ,Variant Genotypes ,Research and Analysis Methods ,Mathematical and Statistical Techniques ,Cell Signaling ,Genetics ,Genome-Wide Association Studies ,Medicine and Health Sciences ,Statistical Methods ,Biology and Life Sciences ,Computational Biology ,Human Genetics ,Genomics ,Cell Biology ,Genome Analysis ,Genetic Mapping ,Phenotypes ,Genetic Loci ,Face ,Physical Sciences ,Anatomy ,Head ,Genomic Signal Processing ,Mathematics ,Statistics (Mathematics) ,Research Article ,Meta-Analysis ,Signal Transduction - 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., Author Summary There is a great deal of evidence that genes influence facial appearance. This is perhaps most apparent when we look at our own families, since we are more likely to share facial features in common with our close relatives than with unrelated individuals. Nevertheless, little is known about how variation in specific regions of the genome relates to the kinds of distinguishing facial characteristics that give us our unique identities, e.g., the size and shape of our nose or how far apart our eyes are spaced. In this paper, we investigate this question by examining the association between genetic variants across the whole genome and a set of measurements designed to capture key aspects of facial form. We found evidence of genetic associations involving measures of eye, nose, and facial breadth. In several cases, implicated regions contained genes known to play roles in embryonic face formation or in syndromes in which the face is affected. Our ability to connect specific genetic variants to ubiquitous facial traits can inform our understanding of normal and abnormal craniofacial development, provide potential predictive models of evolutionary changes in human facial features, and improve our ability to create forensic facial reconstructions from DNA.
- Published
- 2016