Facial Wrinkling
Facial wrinkling is a common characteristic of human aging, marked by the formation of folds and lines on the face. While often associated with the natural aging process, the development and severity of facial wrinkles are influenced by a complex interplay of genetic predispositions and environmental factors. Understanding the underlying mechanisms of facial morphology, including wrinkle formation, is a growing area of scientific inquiry.
The biological basis of facial wrinkling involves changes in the skin’s structure, such as the degradation of collagen and elastin fibers, reduced skin elasticity, and repetitive muscle contractions. Genetic factors play a significant role in determining individual differences in facial features, with studies estimating the heritability of facial phenotypes to be between 60% and 90%[1]. Genome-Wide Association Studies (GWAS) and other genomic methodologies are increasingly employed to identify specific genetic variants, such as single-nucleotide polymorphisms (SNPs), associated with various aspects of facial morphology[2]. These studies aim to uncover the genetic architecture of the human face, including interactions between genes like PRICKLE1 and FOCAD [3]. However, the complex nature of facial phenotypes means that the effect of any single gene can be challenging to isolate, as features often represent a complicated mix of local and global shape characteristics [4].
Clinically, an understanding of facial morphology is relevant beyond cosmetic considerations. Facial features are utilized in forensics for human identification and ancestry estimation[1]. Research into the genetic basis of facial variation also contributes to a deeper understanding of developmental dysmorphologies, where specific gene mutations can lead to significant alterations in facial appearance [1]. Advances in this field may eventually inform personalized approaches to dermatological care and anti-aging strategies.
Socially, facial features play a crucial role in human interaction. The diversity of human faces is thought to have evolved partly to facilitate individual recognition, which is fundamental to social engagement [1]. Facial wrinkles can influence perceptions of age, health, and attractiveness, impacting self-image and societal interactions. Consequently, the cosmetic industry places significant emphasis on treatments and products aimed at reducing or preventing facial wrinkles. Ongoing research into the genetic underpinnings of facial wrinkling promises to offer new insights into both the biological processes of aging and the social aspects of human appearance.
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of facial wrinkling, like other complex facial traits, presents several methodological and interpretative challenges that warrant careful consideration. These limitations stem from the inherent complexity of facial morphology, the diversity of human populations, and the practical constraints of large-scale genetic studies.
Phenotyping and Replication Challenges
Section titled “Phenotyping and Replication Challenges”A significant limitation in the study of facial traits, including wrinkling, arises from the lack of consistent phenotyping methods across different research cohorts [5]. The diverse approaches used to generate and analyze facial shape phenotypes, involving varying imaging modalities, landmarking protocols, and measurement types, make it difficult to compare results and often hinder the independent replication of findings [4]. While quantitative measures are theoretically expected to offer higher statistical power, they have not always led to robust associations compared to simpler, univariate tests, and more complex multivariate analyses of facial shape have shown limited success in genome-wide association studies (GWAS) to date [6]. This inconsistency in phenotyping methods can dilute genetic signals and obscure true associations, complicating the comprehensive mapping of genetic influences on facial wrinkling.
Study Design and Statistical Power
Section titled “Study Design and Statistical Power”The genetic architecture of facial traits is complex, with many genes contributing small effects, which poses challenges for study design and statistical power. The effect of any single gene on a complex phenotype like facial wrinkling can be diluted because the observable traits represent an intricate mix of local and global shape features[4]. Individual genetic variants typically explain only a small percentage of the overall trait variance, often less than one percent, which necessitates very large sample sizes to achieve sufficient statistical power for robust discovery and to avoid potential effect-size inflation in smaller studies[7]. Furthermore, while studies often adjust for covariates such as age, restricted age ranges—particularly samples comprising children and adolescents whose faces are still developing—can introduce noise and reduce the power to detect genetic associations, even if they do not typically lead to false positive signals [3].
Generalizability and Genetic Complexity
Section titled “Generalizability and Genetic Complexity”The generalizability of findings across different populations is a critical concern, as genetic associations identified in one ancestral group may not fully translate to others due to variations in genetic architecture and allele frequencies [3]. This highlights the need for diverse cohorts to ensure that the identified genetic factors are broadly applicable to human facial variation. Moreover, facial wrinkling, like other complex facial traits, is influenced not only by individual genetic variants but also by intricate gene-gene interactions (epistasis) and gene-environment interactions, many of which remain largely unexplored[3]. This complex interplay contributes to the phenomenon of “missing heritability,” where the proportion of trait variance explained by identified genetic variants is less than the estimated total heritability. Fully understanding the genetic basis of facial wrinkling will require extensive fine mapping and detailed investigations to identify causal variants and their specific effects within genomic regions[8].
Variants
Section titled “Variants”Genetic variations play a crucial role in influencing an individual’s predisposition to various facial traits, including the development of facial wrinkling. These variations often affect genes involved in fundamental biological processes such as cellular regulation, tissue maintenance, and environmental response, all of which contribute to skin health and aging. Genome-wide association studies (GWAS) have identified numerous genetic loci associated with facial morphology and skin-related traits, underscoring the complex interplay of genetics and appearance.
Several variants, including rs10476781 near LINC01933 and NMUR2, rs11213999 in PPP2R1B, and rs62047859 near LINC02125, are implicated in pathways relevant to skin integrity. LINC01933 and LINC02125are long intergenic non-coding RNAs (lncRNAs), which are pivotal regulators of gene expression, influencing cellular processes like growth, differentiation, and repair. Variants in these lncRNAs can alter their stability or interactions, potentially disrupting gene networks essential for maintaining youthful skin and affecting its resilience against aging.NMUR2encodes a receptor for neuromedin U, a neuropeptide involved in inflammation and stress responses, which are key drivers of skin aging and wrinkle formation. A variant inNMUR2 could modulate receptor activity, thereby influencing these neuro-cutaneous interactions. Similarly, PPP2R1B is a component of protein phosphatase 2A (PP2A), a major enzyme that regulates cell growth and signal transduction. Proper PP2A function is vital for processes like collagen synthesis and elastin maintenance, making variants in PPP2R1B potentially impactful on skin elasticity and the appearance of wrinkles.
Further genetic contributions to facial morphology and skin aging are seen with variants such asrs147672305 in RIMS2, rs78569750 in CELF4, and rs6429657 associated with KAZN and KAZN-AS1. RIMS2is primarily known for its role in regulating neurotransmitter release, and while its direct link to skin aging is indirect, neuro-cutaneous interactions can affect skin health and resilience over time.CELF4 is an RNA-binding protein that controls mRNA stability and translation, playing a broad role in gene expression. Variants affecting CELF4 could alter the synthesis of crucial skin proteins, including collagen and elastin, thereby influencing skin structure and wrinkle formation. KAZN is a protein essential for keratinocyte differentiation and skin barrier function, providing protection against environmental damage, a major accelerator of wrinkling. The antisense RNA KAZN-AS1 likely regulates KAZN expression. Thus, variants like rs6429657 could impair the skin’s protective barrier, increasing susceptibility to environmental stressors and accelerating the visible signs of aging[4].
The genetic landscape of facial features also includes rs1283106 near DUBR and CCDC54-AS1, rs702491 in GLIS1, rs1225927 in BMP6, and rs116248825 near VENTXP4 and LRRC3B-AS1. DUBRis a deubiquitinase enzyme that regulates protein stability, a process critical for cellular protein quality control and stress response. Dysregulation by a variant could lead to compromised cellular repair and accelerated skin aging.GLIS1 is a transcription factor involved in stem cell pluripotency and regeneration. A variant in GLIS1 might affect the skin’s regenerative capacity, diminishing its ability to repair damage and maintain a youthful appearance. BMP6, a member of the TGF-β superfamily, is involved in wound healing and epidermal differentiation, influencing fibroblast activity and extracellular matrix production. Variations in BMP6 could alter these signaling pathways, affecting collagen production and skin thickness. Lastly, VENTXP4 and LRRC3B-AS1 are non-coding RNA genes. Variants in these regions, such as rs116248825 , can impact the expression of nearby genes or broader RNA-mediated regulatory networks vital for skin cell function and resistance to aging, thereby influencing the development of facial wrinkles[6].
Key Variants
Section titled “Key Variants”Defining Facial Wrinkling and Related Terminology
Section titled “Defining Facial Wrinkling and Related Terminology”Facial wrinkling, as a notable characteristic of facial appearance, represents a specific facial phenotype that can be precisely defined and quantified for scientific investigation. A particular manifestation addressed in research is “fine wrinkle depth,” which refers to the quantifiable measure of the shallow creases or folds in the skin’s surface . These manifestations encompass both local and global shape features, affecting specific facial segments such as the lower lip height[4]. The presentation patterns can range widely, from subtle differences in feature dimensions to distinct early age facial growth patterns [9]. This inherent heterogeneity is a fundamental characteristic of human facial morphology, contributing significantly to individual recognition[1].
Quantitative Assessment of Facial Morphology
Section titled “Quantitative Assessment of Facial Morphology”Objective assessment of facial features relies heavily on advanced methodologies such as 3D facial phenotyping, which can be applied in contexts like biometric sibling matching for comprehensive analysis [10]. These methods generate detailed 3D facial surface models, allowing for precise quantification of various craniofacial traits and specific facial segments [4]. Researchers also employ machine-learning algorithms, such as support vector regression, to predict facial phenotypes based on genotypic markers, enhancing the diagnostic and predictive capabilities [2]. These quantitative approaches provide a robust framework for assessing the complex mix of local and global facial shape features [4].
Genetic Contributions and Clinical Correlates of Facial Traits
Section titled “Genetic Contributions and Clinical Correlates of Facial Traits”The underlying genetic architecture significantly influences the presentation and variability of facial features, with heritabilities estimated to be between 60% and 90% for various facial phenotypes [1]. Genome-wide association studies (GWAS) have identified numerous genetic loci and specific genes, such as DCHS2, RUNX2, GLI3, PAX1, and EDAR, that contribute to normal human facial morphology and variation[1]. This genetic understanding holds diagnostic value, particularly in forensic science for human identification and ancestry estimation, and informs the molecular basis of variable facial appearance [1]. The identification of regulatory variants, for example, those influencing eyebrow thickness, further illustrates the precise genetic control over specific facial traits [11].
Biological Background for Facial Wrinkling
Section titled “Biological Background for Facial Wrinkling”Genetic Architecture of Facial Morphology
Section titled “Genetic Architecture of Facial Morphology”Human facial features display a wide range of variations, a characteristic significantly influenced by an individual’s genetic makeup, with heritability estimates for facial phenotypes often falling between 60% and 90% [1]. Genome-wide association studies (GWAS) have been instrumental in identifying numerous genetic loci and single nucleotide polymorphisms (SNPs) that are associated with normal human facial morphology[4]. These investigations have revealed a complex genetic architecture, implicating specific genes such as DCHS2, RUNX2, GLI3, PAX1, and EDAR in contributing to human facial variation [1].
Further research has highlighted the roles of additional genes like UBE2O and TPK1in influencing facial morphology, particularly in specific populations[12]. The interplay between genetic variants is also crucial, as evidenced by interactions such as that between PRICKLE1 and FOCAD, which affect facial traits [3]. Many identified SNPs are located in regions with regulatory functions, suggesting that precise gene expression patterns and their regulation are key determinants of facial appearance [8].
Developmental Foundations of Facial Structure
Section titled “Developmental Foundations of Facial Structure”The intricate formation of the face originates during embryonic stages, primarily involving cranial neural crest cells (CNCCs) and various craniofacial tissues [8]. Signaling pathways are crucial in orchestrating this complex developmental process; for instance, BMP (Bone Morphogenetic Protein) signaling regulates a dose-dependent transcriptional program that is essential for the development of the facial skeleton[12]. Disruptions in these precise developmental pathways or the presence of rare genetic variants can lead to dysmorphologies, underscoring the strong genetic control over facial formation [1].
A deeper understanding of these developmental events is provided by high-resolution epigenomic atlases of human embryonic craniofacial development, which map the regulatory landscape that influences facial formation [13]. These epigenetic modifications and regulatory elements precisely control gene expression patterns, thereby shaping the initial formation and subsequent maturation of facial structures [3]. The coordinated interaction between an individual’s genetic predispositions and these complex developmental pathways lays the groundwork for their unique facial morphology.
Molecular and Cellular Regulation of Facial Appearance
Section titled “Molecular and Cellular Regulation of Facial Appearance”At the molecular and cellular level, specific proteins, enzymes, receptors, and transcription factors act as critical biomolecules that govern facial morphology. Genes identified through GWAS, such asDCHS2, RUNX2, GLI3, PAX1, and EDAR, are often involved in fundamental cellular functions and regulatory networks that contribute to both facial development and its variation [1]. For example, RUNX2is a well-known transcription factor vital for bone formation, highlighting its direct relevance to the structural features of the face.
Investigations are ongoing into the specific cellular functions associated with regions surrounding identified SNPs, aiming to clarify how genetic variations translate into observable facial traits [8]. These functions encompass crucial processes such as cell differentiation, proliferation, migration, and programmed cell death, all of which are precisely coordinated during craniofacial development. Furthermore, regulatory elements, including non-coding SNPs, exert significant control over gene expression, influencing the quantity and timing of protein production, which in turn fine-tunes the development and maintenance of facial tissues [3].
Tissue-Level Organization and Facial Variation
Section titled “Tissue-Level Organization and Facial Variation”The human face is a highly complex structure, formed by the intricate interactions of multiple tissues and organs, including bone, cartilage, muscle, fat, and skin. Variations in facial morphology can be effectively analyzed by dividing the face into distinct segments, with different genetic loci influencing specific regions[3]. This segmented approach enables a more detailed understanding of how genetic variants exert localized effects on features such as the nose, eyes, or lips.
The broader implications of gene function are evident in the coordinated development of these facial segments and their collective contribution to overall facial appearance [8]. For instance, genes that influence skeletal development directly impact the underlying bone structure, which subsequently dictates the contours of the overlying soft tissues. A comprehensive analysis of these tissue interactions and organ-specific effects is therefore essential for fully elucidating the wide spectrum of normal human facial variation[1].
The manifestation of facial wrinkling is intricately linked to the underlying morphology and structural integrity of the face, which are themselves products of complex developmental and maintenance pathways. Genetic predispositions, epigenetic modifications, and the dynamic interplay of signaling networks collectively establish the architecture that influences how facial skin ages and wrinkles over time. Understanding these foundational pathways provides insight into the variability of facial features and their susceptibility to age-related changes.
Genetic and Epigenetic Orchestration of Facial Architecture
Section titled “Genetic and Epigenetic Orchestration of Facial Architecture”The fundamental blueprint for facial morphology, which forms the substrate for facial wrinkling, is encoded within an individual’s genome and modulated by epigenetic mechanisms. Genome-wide association studies (GWAS) have identified numerous genetic variants, primarily single-nucleotide polymorphisms (SNPs), that are associated with the diverse array of human facial traits[3]. These variants can be located in both coding and non-coding regions of the genome, with non-coding SNPs often exerting significant regulatory control over gene expression, thereby shaping facial development [3]. The precise dosage of transcription factors is particularly critical, as even subtle alterations in their levels can lead to dosage sensitivity and impact facial morphology[14].
Beyond the genetic sequence, epigenetic modifications play a crucial role in establishing and maintaining the specific gene expression patterns required for craniofacial development. High-resolution epigenomic atlases of human embryonic craniofacial development reveal the dynamic landscape of these modifications, including DNA methylation and histone modifications, which influence chromatin accessibility and gene transcription[12]. These epigenetic programs ensure the proper spatiotemporal expression of genes involved in tissue formation and patterning, fine-tuning the developmental pathways that contribute to the face’s intricate structure and, consequently, its susceptibility to wrinkling.
Signaling Cascades and Developmental Control
Section titled “Signaling Cascades and Developmental Control”The development of facial structures is orchestrated by a series of interconnected signaling pathways that translate external and internal cues into precise cellular responses. Receptor activation on cell surfaces initiates intracellular signaling cascades, which propagate biochemical signals through the cytoplasm and ultimately regulate gene expression and cellular behavior. These cascades ensure that cells differentiate, proliferate, and migrate in a coordinated manner to form the complex craniofacial tissues.
A key example is Bone Morphogenetic Protein (BMP) signaling, which regulates a dose-dependent transcriptional program essential for the development of the facial skeleton[12]. This pathway’s intricate feedback loops and interactions with other signaling networks ensure the correct patterning and growth of bones and cartilages that define facial contours. Dysregulation within these critical signaling cascades can lead to significant variations in facial morphology, influencing the mechanical properties and underlying support of the skin that ultimately affects wrinkling.
Interconnected Genetic Networks and Regulatory Integration
Section titled “Interconnected Genetic Networks and Regulatory Integration”Facial morphology and its predisposition to wrinkling emerge not from the action of isolated genes, but from the complex interplay and crosstalk among multiple genetic pathways. Genetic variants frequently exhibit joint and interaction effects, as evidenced by studies revealing specific interactions such as that betweenPRICKLE1 and FOCAD in influencing human facial traits [3]. Other genes, including FREM1, PARK2, UBE2O, and TPK1, have also been identified as contributing to facial morphology, highlighting their roles within broader regulatory networks[5].
These network interactions ensure a hierarchically regulated and coordinated developmental program, where the output of one pathway can modulate or be modulated by others, leading to the emergent properties of a cohesive facial phenotype. Beyond transcriptional regulation, post-translational modifications of proteins further fine-tune their activity, stability, and interactions within these complex networks. Such intricate regulatory mechanisms collectively contribute to the structural integrity and dynamic properties of facial tissues, thereby impacting the manifestation and progression of facial wrinkling over time.
Systems-Level Integration and Phenotypic Manifestation
Section titled “Systems-Level Integration and Phenotypic Manifestation”The vast diversity observed in human facial features, which inherently sets the stage for individual patterns of facial wrinkling, results from the cumulative effects and systems-level integration of these genetic, epigenetic, and signaling pathways. Variations in the components or regulatory mechanisms of these pathways can lead to subtle yet distinct differences in facial morphology[4]. For instance, specific regulatory variants, identified through advanced techniques like CRISPR/Cas9-mediated gene editing, have been shown to influence particular facial features such as eyebrow thickness, demonstrating the molecular precision underlying phenotypic variation [11].
Understanding how these individual genetic and regulatory effects integrate across local and global facial shape features is crucial for comprehending the emergent properties of the human face. Advanced 3D facial phenotyping and biometric analyses are essential tools for capturing the full complexity of these interactions and their impact on overall facial architecture [10]. Insights into these integrated systems and how pathway dysregulation contributes to phenotypic variation can ultimately inform the development of therapeutic or aesthetic interventions aimed at influencing facial structure and mitigating the appearance of wrinkling.
Frequently Asked Questions About Facial Wrinkling
Section titled “Frequently Asked Questions About Facial Wrinkling”These questions address the most important and specific aspects of facial wrinkling based on current genetic research.
1. Why do I get wrinkles sooner than my friends?
Section titled “1. Why do I get wrinkles sooner than my friends?”It’s likely due to your unique genetic predisposition. Studies show that facial features, including how quickly and severely you wrinkle, are highly heritable, often between 60% and 90%. This means your genes play a significant role in your skin’s structure and how it responds to aging compared to others. Environmental factors also contribute, but your inherent genetic makeup is a major determinant.
2. My mom has lots of wrinkles; will I get them too?
Section titled “2. My mom has lots of wrinkles; will I get them too?”There’s a strong chance you’ll have a similar tendency, as facial wrinkling is highly heritable, meaning it runs in families. Your genes influence the degradation of collagen and elastin, affecting skin elasticity and how your face forms lines. However, environmental factors like sun exposure and lifestyle choices also play a role, so your wrinkles might not be identical to hers.
3. Can I prevent wrinkles even if they run in my family?
Section titled “3. Can I prevent wrinkles even if they run in my family?”While your genetics strongly predispose you to wrinkling, influencing between 60% and 90% of facial traits, you can definitely influence their severity and onset. Environmental factors like consistent sun protection, good hydration, and overall skin care are crucial. These actions can help mitigate your genetic tendency, even if you can’t entirely prevent wrinkle formation.
4. Does what I eat or do really matter for wrinkles?
Section titled “4. Does what I eat or do really matter for wrinkles?”Yes, absolutely. While genetics play a significant role in your inherent predisposition to wrinkles, environmental factors and lifestyle choices directly impact their development and severity. Things like sun exposure, diet, and repetitive muscle contractions can accelerate the breakdown of collagen and elastin, making wrinkles appear more pronounced. It’s a complex interplay between your genes and your daily habits.
5. Could a genetic test tell me how much I’ll wrinkle?
Section titled “5. Could a genetic test tell me how much I’ll wrinkle?”In the future, genetic tests may offer more specific insights into your predisposition for wrinkling. Researchers are identifying specific genetic variants, like single-nucleotide polymorphisms (SNPs), associated with facial features and skin aging. However, facial wrinkling is complex, influenced by many genes with small effects and their interactions, so current tests might offer general predispositions rather than precise predictions.
6. Does my ancestry affect how my face wrinkles?
Section titled “6. Does my ancestry affect how my face wrinkles?”Yes, your ancestral background can influence your facial features and how you wrinkle. Genetic associations for facial traits can vary across different populations due to diverse genetic architectures and allele frequencies. This means specific genetic factors contributing to wrinkling might be more common or have different effects in certain ethnic groups, highlighting the need for diverse research.
7. Why do some people just seem to age more gracefully?
Section titled “7. Why do some people just seem to age more gracefully?”A significant part of “graceful aging” in terms of wrinkles is attributed to genetics, with facial features being 60-90% heritable. Some individuals naturally have genes that support better collagen and elastin maintenance or stronger skin elasticity. While lifestyle choices certainly play a role, their genetic makeup can give them a natural advantage in maintaining a youthful appearance longer.
8. My sibling and I look different; why do our wrinkles vary?
Section titled “8. My sibling and I look different; why do our wrinkles vary?”Even with shared genetics, individual differences in facial wrinkling can arise due to a complex interplay of factors. While facial traits are highly heritable, specific genetic variants can combine uniquely in each sibling, leading to subtle differences. Additionally, varying environmental exposures and lifestyle choices, even within the same family, contribute to how wrinkles manifest.
9. Is there one ‘wrinkle gene’ I should worry about?
Section titled “9. Is there one ‘wrinkle gene’ I should worry about?”No, there isn’t a single “wrinkle gene” that dictates everything. Facial wrinkling is a complex trait influenced by many genes, each contributing a small effect. Researchers are identifying various genetic variants and even gene interactions, like those involvingPRICKLE1 and FOCAD, but it’s the intricate combination of these genes and environmental factors that determines your wrinkle pattern.
10. Can knowing my genes help me pick better anti-wrinkle products?
Section titled “10. Can knowing my genes help me pick better anti-wrinkle products?”Potentially, yes. Advances in understanding the genetic basis of facial variation may eventually inform personalized dermatological care and anti-aging strategies. If genetic tests can pinpoint your specific predispositions, such as tendencies for collagen degradation or reduced elasticity, it could guide recommendations for products or treatments tailored to your unique genetic profile.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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