Int J Stomatol

Int J Stomatol ›› 2024, Vol. 51 ›› Issue (6): 728-735.doi: 10.7518/gjkq.2024055

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Advancements in genome-wide association study-based genetic analysis of human craniofacial morphology

Xin Hou1,2(),Jiewen Dai2()   

  1. 1.School of Stomatology, Shandong Second Medical University, Weifang 261053, China
    2.Dept. of Oral and Cranioma-xillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
  • Received:2023-12-08 Revised:2024-04-02 Online:2024-11-01 Published:2024-11-04
  • Contact: Jiewen Dai E-mail:h2250045863@163.com;daijiewen@163.com
  • Supported by:
    National Natural Science Foundation of China(82071097);Shanghai Municipal Health Commission Excellence Project(20234Z0006)

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Abstract:

The complexity of facial morphology, influenced by various factors, endows human facial features with distinctive characteristics. Following the completion of the Human Genome Project and the advent of affordable, high-resolution imaging systems, the scientific community has increasingly focused on analyzing the genetic underpinnings of normal facial features, particularly the relevant genetic loci and biological mechanisms. This paper examines the genetic associations influencing normal human facial morphology, offers a comprehensive review of the advancements in craniofacial genetics through genome-wide association studies, and assesses the facial genetic variability across different populations. This work not only elucidates the mechanisms underlying craniofacial developmental anomalies but also enhances the accuracy and security of facial recognition technologies. Furthermore, it facilitates the use of genetic data in forensic science to reconstruct facial appearances of individuals, thereby contributing to criminal investigations and advancing our understanding of human evolution.

Key words: genetics, facial shape, genome-wide association study

CLC Number: 

  • Q786

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Fig 1

Known genes associated with facial features in normal populations"

1 Paternoster L, Zhurov AI, Toma AM, et al. Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 associated with nasion position[J]. Am J Hum Genet, 2012, 90(3): 478-485.
2 Long HK, Osterwalder M, Welsh IC, et al. Loss of extreme long-range enhancers in human neural crest drives a craniofacial disorder[J]. Cell Stem Cell, 2020, 27(5): 765-783.e14.
3 Gokhman D, Mishol N, de Manuel M, et al. Reconstructing denisovan anatomy using DNA methylation maps[J]. Cell, 2020, 180(3): 601.
4 Jheon AH, Oberoi S, Solem RC, et al. Moving towards precision orthodontics: an evolving paradigm shift in the planning and delivery of customized orthodontic therapy[J]. Orthod Craniofac Res, 2017, 20(): 106-113.
5 Claes P, Liberton DK, Daniels K, et al. Modeling 3D facial shape from DNA[J]. PLoS Genet, 2014, 10(3): e1004224.
6 Kau CH, Richmond S, Zhurov A, et al. Use of 3-dimensional surface acquisition to study facial morphology in 5 populations[J]. Am J Orthod Dentofacial Orthop, 2010, 137(4 ): S56.e1-S56.e9.
7 Matthews HS, Penington AJ, Hardiman R, et al. Modelling 3D craniofacial growth trajectories for population comparison and classification illustrated using sex-differences[J]. Sci Rep, 2018, 8(1): 4771.
8 Hammond P. The use of 3D face shape modelling in dysmorphology[J]. Arch Dis Child, 2007, 92(12): 1120-1126.
9 Liu F, van der Lijn F, Schurmann C, et al. A genome-wide association study identifies five loci influencing facial morphology in Europeans[J]. PLoS Genet, 2012, 8(9): e1002932.
10 Tsagkrasoulis D, Hysi P, Spector T, et al. Heritability maps of human face morphology through large-scale automated three-dimensional phenotyping[J]. Sci Rep, 2017, 7: 45885.
11 Hoskens H, Li JR, Indencleef K, et al. Spatially dense 3D facial heritability and modules of co-heritability in a father-offspring design[J]. Front Genet, 2018, 9: 554.
12 Cole JB, Manyama M, Larson JR, et al. Human facial shape and size heritability and genetic correlations[J]. Genetics, 2017, 205(2): 967-978.
13 Hoskens H, Liu DJ, Naqvi S, et al. 3D facial phenotyping by biometric sibling matching used in contemporary genomic methodologies[J]. PLoS Genet, 2021, 17(5): e1009528.
14 Adhikari K, Fuentes-Guajardo M, Quinto-Sánchez M, et al. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation[J]. Nat Commun, 2016, 7: 11616.
15 Zhang MF, Wu SJ, Du SY, et al. Genetic variants underlying differences in facial morphology in East Asian and European populations[J]. Nat Genet, 2022, 54(4): 403-411.
16 Bonfante B, Faux P, Navarro N, et al. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation[J]. Sci Adv, 2021, 7(6): eabc-6160.
17 Cole JB, Manyama M, Kimwaga E, et al. Genomewide association study of African children identifies association of SCHIP1 and PDE8A with facial size and shape[J]. PLoS Genet, 2016, 12(8): e1006174.
18 White JD, Indencleef K, Naqvi S, et al. Insights into the genetic architecture of the human face[J]. Nat Genet, 2021, 53(1): 45-53.
19 Li Q, Chen JY, Faux P, et al. Automatic landmar-king identifies new loci associated with face morpho-logy and implicates Neanderthal introgression in human nasal shape[J]. Commun Biol, 2023, 6(1): 481.
20 Djordjevic J, Zhurov AI, Richmond S. Genetic and environmental contributions to facial morphologi-cal variation: a 3D population-based twin study[J]. PLoS One, 2016, 11(9): e0162250.
21 Kuijpers MA, Chiu YT, Nada RM, et al. Three-dimensional imaging methods for quantitative analysis of facial soft tissues and skeletal morphology in patients with orofacial clefts: a systematic review[J]. PLoS One, 2014, 9(4): e93442.
22 Salvoro C, Faccinetto C, Zucchelli L, et al. Performance of four models for eye color prediction in an Italian population sample[J]. Forensic Sci Int Genet, 2019, 40: 192-200.
23 Cha S, Lim JE, Park AY, et al. Identification of five novel genetic loci related to facial morphology by genome-wide association studies[J]. BMC Geno-mics, 2018, 19(1): 481.
24 Farkas LG, Katic MJ, Forrest CR, et al. Internatio-nal anthropometric study of facial morphology in various ethnic groups/races[J]. J Craniofac Surg, 2005, 16(4): 615-646.
25 Claes P, Walters M, Clement J. Improved facial outcome assessment using a 3D anthropometric mask[J]. Int J Oral Maxillofac Surg, 2012, 41(3): 324-330.
26 Claes P, Roosenboom J, White JD, et al. Genome-wide mapping of global-to-local genetic effects on human facial shape[J]. Nat Genet, 2018, 50(3): 414-423.
27 Liu CX, Lee MK, Naqvi S, et al. Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations[J]. PLoS Genet, 2021, 17(8): e1009695.
28 Qiao L, Yang YJ, Fu PC, et al. Genome-wide va-riants of Eurasian facial shape differentiation and a prospective model of DNA based face prediction[J]. J Genet Genomics, 2018, 45(8): 419-432.
29 Huang Y, Li D, Qiao L, et al. A genome-wide asso-ciation study of facial morphology identifies novel genetic loci in Han Chinese[J]. J Genet Genomics, 2021, 48(3): 198-207.
30 Gurovich Y, Hanani Y, Bar O, et al. Identifying facial phenotypes of genetic disorders using deep learning[J]. Nat Med, 2019, 25(1): 60-64.
31 Adhikari K, Reales G, Smith AJ, et al. A genome-wide association study identifies multiple loci for variation in human ear morphology[J]. Nat Commun, 2015, 6: 7500.
32 Xiong ZY, Dankova G, Howe LJ, et al. Novel gene-tic loci affecting facial shape variation in humans[J]. Elife, 2019, 8: e49898.
33 Lee MK, Shaffer JR, Leslie EJ, et al. Genome-wide association study of facial morphology reveals no-vel associations with FREM1 and PARK2[J]. PLoS One, 2017, 12(4): e0176566.
34 Crouch DJM, Winney B, Koppen WP, et al. Gene-tics of the human face: identification of large-effect single gene variants[J]. Proc Natl Acad Sci U S A, 2018, 115(4): E676-E685.
35 Boudjadi S, Chatterjee B, Sun W, et al. The expression and function of PAX3 in development and di-sease[J]. Gene, 2018, 666: 145-157.
36 Lacruz RS, Stringer CB, Kimbel WH, et al. The evolutionary history of the human face[J]. Nat Ecol Evol, 2019, 3(5): 726-736.
37 Fumagalli M, Moltke I, Grarup N, et al. Greenlan-dic Inuit show genetic signatures of diet and climate adaptation[J]. Science, 2015, 349(6254): 1343-1347.
38 Shaffer JR, Orlova E, Lee MK, et al. Genome-wide association study reveals multiple loci influencing normal human facial morphology[J]. PLoS Genet, 2016, 12(8): e1006149.
39 Boehringer S, van der Lijn F, Liu F, et al. Genetic determination of human facial morphology: links between cleft-lips and normal variation[J]. Eur J Hum Genet, 2011, 19(11): 1192-1197.
40 Indencleef K, Roosenboom J, Hoskens H, et al. Six NSCL/P loci show associations with normal-range craniofacial variation[J]. Front Genet, 2018, 9: 502.
41 McLean CY, Bristor D, Hiller M, et al. GREAT improves functional interpretation of cis-regulatory regions[J]. Nat Biotechnol, 2010, 28(5): 495-501.
42 Attanasio C, Nord AS, Zhu YW, et al. Fine tuning of craniofacial morphology by distant-acting enhan-cers[J]. Science, 2013, 342(6157): 1241006.
43 Winter RM. What’s in a face[J]. Nat Genet, 1996, 12(2): 124-129.
44 Kraus P, Lufkin T. Dlx homeobox gene control of mammalian limb and craniofacial development[J]. Am J Med Genet A, 2006, 140(13): 1366-1374.
45 Tak YG, Farnham PJ. Making sense of GWAS: u-sing epigenomics and genome engineering to understand the functional relevance of SNPs in non-co-ding regions of the human genome[J]. Epigenetics Chromatin, 2015, 8: 57.
46 Ludwig KU, Böhmer AC, Bowes J, et al. Imputation of orofacial clefting data identifies novel risk loci and sheds light on the genetic background of cleft lip ± cleft palate and cleft palate only[J]. Hum Mol Genet, 2017, 26(4): 829-842.
47 Visser M, Palstra RJ, Kayser M. Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter[J]. Hum Mol Genet, 2015, 24(9): 2649-2661.
48 Visser M, Kayser M, Palstra RJ. HERC2 rs1291-3832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter[J]. Genome Res, 2012, 22(3): 446-455.
49 Visser M, Palstra RJ, Kayser M. Human skin color is influenced by an intergenic DNA polymorphism regulating transcription of the nearby BNC2 pigmentation gene[J]. Hum Mol Genet, 2014, 23(21): 5750-5762.
50 Bronner ME, LeDouarin NM. Development and evolution of the neural crest: an overview[J]. Dev Biol, 2012, 366(1): 2-9.
51 Green SA, Simoes-Costa M, Bronner ME. Evolution of vertebrates as viewed from the crest[J]. Nature, 2015, 520(7548): 474-482.
52 Prescott SL, Srinivasan R, Marchetto MC, et al. Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest[J]. Cell, 2015, 163(1): 68-83.
53 Long HK, Prescott SL, Wysocka J. Ever-changing landscapes: transcriptional enhancers in development and evolution[J]. Cell, 2016, 167(5): 1170-1187.
54 Choi J, Lysakovskaia K, Stik G, et al. Evidence for additive and synergistic action of mammalian enhancers during cell fate determination[J]. Elife, 2021, 10: e65381.
55 Moorthy SD, Davidson S, Shchuka VM, et al. Enhancers and super-enhancers have an equivalent re-gulatory role in embryonic stem cells through regulation of single or multiple genes[J]. Genome Res, 2017, 27(2): 246-258.
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