Fibroblast growth factor receptor 1 (<i>FGFR1</i>) variants and craniofacial variation in Amerindians and related populations

Gómez-Valdés, Jorge; Hünemeier, Tábita; Contini, Verônica; Acuña-Alonzo, Víctor; Macin, Gastón; Ballesteros-Romero, Mónica; Corral, Pau; Ruiz-Linares, Andrés; Sánchez‐Mejorada, Gabriela; Canizales‐Quinteros, Samuel; Martínez‐Abadías, Neus; Salzano, Francisco M.; González‐José, Rolando; Bortolini, María Cátira

doi:10.1002/ajhb.22331

Cited by 12 publications

(16 citation statements)

References 32 publications

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“…In addition, several more focused candidate gene studies of loci implicated in craniofacial syndromes or in developmental pathways involved in craniofacial development have connected one or more craniofacial dimensions or aspects of shape with a small number of common genetic variants [19–28]. At least three candidate gene studies [20,25,28] have reported modest associations between common variants in FGFR1 and normal variation in craniofacial morphology, but in each case a different constellation of traits was involved. It is notable that none of the genes from these studies, including FGFR1 , were identified in the two previous GWA studies of facial morphology.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

et al. 2016

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“…FGFR1 , the fibroblast growth factor receptor 1 plays an important role in facial morphogenesis, and mutations in this gene lead to syndomes associated with facial abnormality, such as the type 1 Pfeiffer syndrome (MIM 101600) and Kallmann syndrome 2 (KAL2) (MIM 147950) [34]. A tagging SNP of this gene, rs4647905 showed moderate signals of association with cephalic index in multiple ethnic groups [43]. We added another tagging SNP rs3213849 to span the full length of FGFR1 .…”

Section: Resultsmentioning

confidence: 99%

Detecting Genetic Association of Common Human Facial Morphological Variation Using High Density 3D Image Registration

Peng¹,

Tan

Hu³

et al. 2013

PLoS Comput Biol

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Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.

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“…Gómezvaldés et al [15] evaluated the relationships between FGFR1 polymorphisms and cephalometric measurements and indices in one Mexican Native and two mestizo Mexican populations, and found a tendency for a decrease in cephalic index in individuals homozygous for the allele rs4647905C; when General Linear Model analyses were performed, a statistically significant association was found between four SNPs in FGFR1 and head length in the mestizo population. In our research, we found that there was a significant association between the FGFR1 rs4647905 polymorphism and the linear distance of LLipCn-Nsn, affecting the middle anterior face height, and the distance of the upper lip to the subnasale.…”

Section: Discussionmentioning

confidence: 99%

Correlation between facial morphology and gene polymorphisms in the Uygur youth population

Zhang

et al. 2017

Oncotarget

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Human facial morphology varies considerably among individuals and can be influenced by gene polymorphisms. We explored the effects of single nucleotide polymorphisms (SNPs) on facial features in the Uygur youth population of the Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers, and 10 SNPs previously associated with variations in facial physiognomy were genotyped. In parallel, 3D images of the subjects’ faces were obtained using grating facial scanning technology. After delimitation of 15 salient landmarks, the correlation between SNPs and the distances between facial landmark pairs was assessed. Analysis of variance revealed that ENPP1 rs7754561 polymorphism was significantly associated with RAla-RLipCn and RLipCn-Sbn linear distances (p = 0.044 and p = 0.012, respectively) as well as RLipCn-Stm curve distance (p = 0.042). The GHR rs6180 polymorphism correlated with RLipCn-Stm linear distance (p = 0.04), while the GHR rs6184 polymorphism correlated with RLipCn-ULipP curve distance (p = 0.047). The FGFR1 rs4647905 polymorphism was associated with LLipCn-Nsn linear distance (p = 0.042). These results reveal that ENPP1 and FGFR1 influence lower anterior face height, the distance from the upper lip to the nasal floor, and lip shape. FGFR1 also influences the lower anterior face height, while GHR is associated with the length and width of the lip.

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Fibroblast growth factor receptor 1 (FGFR1) variants and craniofacial variation in Amerindians and related populations

Cited by 12 publications

References 32 publications

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Detecting Genetic Association of Common Human Facial Morphological Variation Using High Density 3D Image Registration

Correlation between facial morphology and gene polymorphisms in the Uygur youth population

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