Abnormality Of The Dentition
Abnormality of the dentition refers to any deviation from the typical development, structure, or alignment of teeth within the oral cavity. These conditions can manifest in various ways, including issues with the number of teeth (e.g., missing teeth or supernumerary teeth), their size (e.g., microdontia or macrodontia), their shape (e.g., peg laterals or fused teeth), their position (e.g., malocclusions, rotations, or impactions), or their structural integrity (e.g., enamel hypoplasia or dentinogenesis imperfecta). Such abnormalities can affect both primary (deciduous) and permanent dentition and range from minor aesthetic concerns to significant functional impairments.
The biological basis of dental abnormalities is complex and often multifactorial, involving an interplay of genetic and environmental factors. Genetic predispositions play a significant role, with many conditions exhibiting hereditary patterns or being associated with specific genetic syndromes. Genes involved in tooth development, enamel formation, and bone growth can all contribute to the manifestation of these abnormalities. Environmental factors, such as trauma, nutritional deficiencies, systemic diseases, and certain medications during critical stages of odontogenesis, can also disrupt normal tooth development.
From a clinical perspective, abnormalities of the dentition can have substantial impacts on an individual’s oral health and overall well-being. They can compromise masticatory function, affect speech articulation, and increase susceptibility to dental caries, periodontal disease, and temporomandibular joint disorders. Early diagnosis and appropriate intervention, often involving orthodontic, restorative, or surgical treatments, are crucial for managing these conditions and preventing further complications.
Beyond clinical implications, dental abnormalities carry significant social importance. The appearance of teeth and the smile play a crucial role in self-esteem, social interaction, and psychological well-being. Visible dental irregularities can lead to self-consciousness, anxiety, and impact an individual’s quality of life. The economic burden associated with the long-term management and treatment of complex dental abnormalities also represents a notable public health concern.
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of dentition abnormalities is complex, and current research faces several inherent limitations. These limitations stem from the methodologies employed in genetic studies, the intricate nature of the trait itself, and the need for broader representation and deeper mechanistic insights. Acknowledging these challenges is crucial for accurate interpretation of findings and for guiding future research directions.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Genetic studies, particularly genome-wide association studies (GWAS), are susceptible to various methodological and statistical constraints that can affect the robustness and generalizability of their findings. Detecting subtle genetic effects for complex traits often requires exceptionally large sample sizes, and smaller cohorts may lead to inflated effect sizes for identified variants, making replication challenging [1]. A persistent challenge across human genetic studies, including those related to craniofacial and dental traits, is the lack of consistent phenotyping across existing cohorts, which complicates independent replication efforts essential for validating initial discoveries [2].
Furthermore, rigorous statistical approaches are critical to mitigate false positives. Adjustments for population stratification, which accounts for genetic differences between subgroups within a study population, are necessary to prevent spurious associations [3]. Studies also typically employ stringent quality control measures, such as filtering single nucleotide polymorphisms (SNPs) based on minor allele frequency or imputation quality, which can inadvertently exclude rare variants that may hold significant biological importance[4]. The application of multiple testing corrections, like Bonferroni or False Discovery Rate (FDR) methods, while vital for maintaining statistical rigor across millions of tested variants, can also lead to a conservative threshold that may obscure true, yet weaker, genetic signals [4].
Phenotypic Heterogeneity and Measurement Challenges
Section titled “Phenotypic Heterogeneity and Measurement Challenges”The trait “abnormality of the dentition” is inherently broad and encompasses a wide spectrum of conditions, from malocclusions and agenesis to structural defects and eruption anomalies. This phenotypic heterogeneity poses a significant challenge, as each specific abnormality likely has a distinct genetic architecture that may be diluted when analyzed as a collective trait. The consistency and standardization of how these diverse dental phenotypes are defined, assessed, and measured across different research cohorts can vary considerably, introducing noise and hindering the ability to combine data effectively in meta-analyses[2].
Subjective or inconsistent measurement protocols can reduce statistical power and obscure true genetic associations. While advancements in automated landmarking methods are being explored for related traits like facial morphology, their comprehensive development and validation for the wide array of dental abnormalities are still evolving, highlighting a current limitation in achieving highly precise and scalable phenotyping[2]. Additionally, specific exclusion criteria in study designs, such as removing participants with a personal or family history of certain conditions, might inadvertently narrow the genetic diversity under investigation and limit the generalizability of findings to the broader population [2].
Ancestry, Environmental Confounders, and Knowledge Gaps
Section titled “Ancestry, Environmental Confounders, and Knowledge Gaps”The generalizability of genetic findings is significantly influenced by the ancestry of the study populations. Many foundational genetic studies have historically been conducted predominantly in populations of European descent, which can limit the direct applicability and transferability of identified genetic variants to other ancestral groups [1]. Genetic architecture, including allele frequencies and linkage disequilibrium patterns, can vary considerably across populations, meaning that variants identified in one group may not exert the same effect or have the same predictive power in another [1].
Furthermore, environmental factors and complex gene-environment interactions play a substantial, yet often unquantified, role in the development of dental abnormalities. Oral hygiene practices, dietary habits, exposure to environmental toxins, and access to dental care are all critical non-genetic influences that can act as confounders or modify genetic predispositions, making it challenging to isolate purely genetic effects. The concept of “missing heritability” suggests that a significant portion of the genetic variation for complex traits remains unexplained by common variants identified in GWAS, pointing to the potential involvement of rare variants, structural variations, or complex epistatic interactions that are not fully captured by current methodologies [4]. These unaddressed factors represent substantial remaining knowledge gaps in fully elucidating the comprehensive etiology of dentition abnormalities.
Variants
Section titled “Variants”Genetic variants play a crucial role in the development and health of the dentition, influencing everything from tooth number and shape to enamel quality and jaw structure. Variations in genes involved in fundamental cellular processes, developmental signaling, and tissue patterning can contribute to a range of dental abnormalities. The variants discussed here are located within or near genes with diverse functions, each potentially impacting the intricate cascade of events required for proper odontogenesis.
Variants such as rs139340401 , associated with the EFR3B gene, and rs6479408 , near SPTLC1, are linked to genes involved in essential cellular functions. EFR3B plays a role in regulating membrane lipid signaling, a process vital for cell growth, differentiation, and trafficking. Disruptions in these fundamental cellular mechanisms can affect the precise coordination needed for tooth bud formation, the deposition of enamel and dentin matrices, and overall tooth development, potentially leading to structural defects or abnormal eruption patterns. Similarly, SPTLC1 is a key enzyme in sphingolipid biosynthesis, which produces crucial components of cell membranes and signaling pathways. Variations here can alter cell signaling during odontogenesis, impacting tooth shape, size, or enamel quality. Thers140220410 variant in ABHD17C, a gene involved in protein deacylation, can affect protein function and localization, which are critical for cell adhesion, signaling, and extracellular matrix remodeling—all indispensable for the proper development of teeth and jawbones.
Other variants, including rs12379966 and rs10511451 in the RFX3-DT region, rs9913511 in NTN1, and rs174814 in ROBO2, are associated with genes that direct critical developmental guidance and signaling pathways. RFX3 is a transcription factor important for ciliogenesis and developmental signaling, including pathways like Hedgehog, which are crucial for craniofacial and dental patterning. Variants can disrupt these signals, potentially leading to anomalies in tooth number, morphology, or eruption. NTN1 encodes Netrin 1, a protein that guides cell migration, particularly neural crest cells, which are the embryonic building blocks for teeth and jawbones. Variants might impair the proper migration and positioning of these cells, contributing to malformed dental arches or misaligned teeth. ROBO2, a receptor in the Slit-Robo pathway, is also critical for guiding cell migration and patterning of craniofacial structures. Genetic variations in ROBO2 can lead to defects in jaw development, tooth position, or alignment, contributing to malocclusions or other structural abnormalities. The rs141429354 variant in UNC13C, primarily known for its role in neurotransmitter release, may also influence broader developmental processes, affecting neural crest cell contributions to craniofacial structures and the innervation of the dentition.
Finally, the rs404727 variant located near RNU6-929P and BMP7 highlights the importance of growth factors and gene regulation in dental development. BMP7 (Bone Morphogenetic Protein 7) is a powerful growth factor essential for bone and tooth formation, regulating the differentiation of cells that form enamel and dentin and influencing overall tooth patterning. Variants affecting BMP7 can cause conditions such as hypodontia (missing teeth), abnormal tooth shape, or enamel hypoplasia. Additionally, non-coding RNA variants likers2251904 in LINC00571 and rs1838002 in LINC02884 represent long intergenic non-coding RNAs that play crucial regulatory roles in gene expression. These non-coding RNAs can influence the timing and levels of protein-coding genes involved in skeletal development, cell proliferation, and differentiation—processes vital for the precise and coordinated stages of odontogenesis and jaw formation. Disruptions in their regulatory functions could contribute to various dental developmental anomalies.
Key Variants
Section titled “Key Variants”Causes
Section titled “Causes”Genetic Predisposition
Section titled “Genetic Predisposition”Genetic factors are recognized as fundamental contributors to the development of various complex traits, including structural and developmental characteristics that could influence dentition. Research widely employs genome-wide association studies (GWAS) to identify specific genetic variants, such as single nucleotide polymorphisms (SNPs), that are associated with complex traits. For instance, such studies have successfully identified loci linked to hip bone geometry[5], facial morphology[6], and even refractive error [7]. These genetic influences often reflect a polygenic architecture, where numerous genes, each contributing a small effect, collectively determine an individual’s susceptibility, rather than relying on a single major gene [7]. Beyond these common variants, rarer Mendelian forms, resulting from mutations in single genes, can lead to more pronounced or syndromic abnormalities. Furthermore, complex gene-gene interactions can modify the expression and impact of individual genetic predispositions, influencing the overall manifestation of a trait [8]. These genetic underpinnings highlight the inherited component in the susceptibility to or development of dentition abnormalities.
Biological Background
Section titled “Biological Background”Abnormalities of the dentition encompass a wide range of conditions affecting the development, structure, and position of teeth, as well as the surrounding craniofacial bones. These conditions often arise from complex interactions between genetic predispositions and environmental factors, impacting fundamental biological processes from early embryonic development through continuous tissue maintenance. Understanding the underlying molecular, cellular, and genetic mechanisms is crucial for comprehending the diverse manifestations of dental abnormalities.
Developmental Origins and Genetic Regulation of Craniofacial Structures
Section titled “Developmental Origins and Genetic Regulation of Craniofacial Structures”The precise formation of the dentition is intricately linked to the overall development of the craniofacial skeleton, which begins early in embryonic life. Genes play a critical role in orchestrating the complex processes that shape the face and jawbones, thereby influencing the environment in which teeth develop. For instance, specific genes like FREM1 have been associated with facial morphology, indicating their importance in the intricate shaping of facial features during embryonic development[6]. FREM1 is crucial for basement membrane adhesion and epithelial-mesenchymal interactions, which are fundamental for proper craniofacial patterning and the formation of the jaw structures supporting dentition. Similarly, Growth Differentiation Factor 5 (GDF5), a signaling molecule known for its role in skeletal development, including joint formation and cartilage, underscores the general importance of such factors in bone and cartilage development, which can impact the craniofacial skeleton and thus dentition[9]. These genes and their associated pathways are critical for establishing the foundational architecture upon which dental structures develop, impacting tooth position, alignment, and jaw relationships.
Molecular and Cellular Pathways in Dentition and Bone Formation
Section titled “Molecular and Cellular Pathways in Dentition and Bone Formation”The development of dentition, known as odontogenesis, relies on highly coordinated molecular and cellular pathways involving complex epithelial-mesenchymal interactions. These pathways regulate cell proliferation, differentiation, and apoptosis, leading to the formation of specialized tissues such as enamel, dentin, cementum, and dental pulp. Key biomolecules, including various growth factors, transcription factors, and signaling molecules, orchestrate these precise events, ensuring the proper size, shape, and number of teeth. Concurrently, the alveolar bone, which supports the teeth, undergoes continuous remodeling throughout life, a process involving osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells)[5]. This homeostatic balance is maintained by regulatory networks involving hormones and local factors that influence bone mineral density and geometry[5]. Disruptions in these intricate metabolic processes or cellular functions can lead to structural weaknesses or abnormal bone architecture, directly impacting tooth eruption, stability, and overall dental alignment.
Tissue Interactions and Pathophysiological Processes
Section titled “Tissue Interactions and Pathophysiological Processes”Abnormalities of the dentition often stem from disruptions in the delicate interactions between various tissues at the organ level, including the dental epithelium, mesenchyme, and surrounding bone and soft tissues. Pathophysiological processes can manifest as developmental defects, such as agenesis (missing teeth), supernumerary teeth, or malformations, arising from errors in early tooth bud formation or eruption pathways. For example, disturbances in bone homeostasis, as observed in studies investigating hip bone geometry, can influence the jawbones, potentially leading to issues like altered alveolar ridge morphology or insufficient bone support for teeth[5]. Such homeostatic disruptions can lead to a cascade of effects, where compensatory responses within these systems, while attempting to maintain function, can sometimes contribute to further abnormalities, such as adaptive bone remodeling that exacerbates malocclusion rather than correcting it.
Genetic Predisposition and Regulatory Networks
Section titled “Genetic Predisposition and Regulatory Networks”Genetic mechanisms play a significant role in predisposing individuals to dentition abnormalities, with numerous genes influencing various aspects of tooth development and craniofacial growth. Genome-wide association studies (GWAS) have identified genetic variants associated with complex traits, indicating that regulatory elements and specific gene expression patterns are crucial in determining phenotypic outcomes [10]. For example, genes like RBFOX1, known as a regulator of tissue-specific splicing, highlight how post-transcriptional modifications can influence the final protein products essential for tissue development and function [11]. Furthermore, epigenetic modifications, such as DNA methylation and histone modifications, provide an additional layer of regulatory control by fine-tuning gene expression without altering the underlying DNA sequence. These modifications can impact the timing and precision of developmental events critical for normal dentition, influencing everything from tooth formation to eruption patterns and overall dental arch alignment.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Genetic Regulation and Developmental Signaling
Section titled “Genetic Regulation and Developmental Signaling”Genetic variations, frequently identified as single nucleotide polymorphisms (SNPs) through genome-wide association studies, are instrumental in shaping intricate signaling pathways that govern tissue development. These genetic loci can influence the expression of genes crucial for forming complex structures, as seen in studies identifying variants associated with facial morphology and hip bone geometry[6]. Such genetic influences are presumed to modulate receptor activation and subsequent intracellular signaling cascades, which in turn regulate transcription factors that orchestrate the precise spatial and temporal expression of genes essential for the formation and patterning of skeletal and craniofacial elements, including the dentition.
Metabolic Homeostasis and Biosynthetic Processes
Section titled “Metabolic Homeostasis and Biosynthetic Processes”The proper development and maintenance of biological tissues, including dentition, are fundamentally dependent on robust metabolic pathways. These pathways are responsible for critical functions such as energy production, the biosynthesis of necessary structural components like extracellular matrix proteins, and the regulated catabolism of cellular waste products. The principle of metabolic regulation and flux control is essential for all complex tissue formation, and genetic variants that influence metabolic genes could therefore impact the availability of necessary building blocks or energy, potentially leading to structural or developmental irregularities [3]. Such mechanisms underpin cellular health and tissue integrity.
Post-Translational Control and Molecular Fine-Tuning
Section titled “Post-Translational Control and Molecular Fine-Tuning”Beyond direct gene regulation, the function of proteins is meticulously controlled through various post-translational modifications and allosteric mechanisms. These regulatory processes are critical for fine-tuning protein activity, mediating protein-protein interactions, and ensuring proper cellular responses during development. Genetic variations can indirectly affect these regulatory layers by altering the structure of modifying enzymes or target proteins, thereby disrupting feedback loops or allosteric control [10]. Such molecular adjustments are essential for the precise assembly and maturation of complex tissues, and their dysregulation can contribute to structural abnormalities.
Integrated Network Dynamics and Disease Relevance
Section titled “Integrated Network Dynamics and Disease Relevance”Biological systems function as highly integrated networks, where different pathways constantly crosstalk and operate under hierarchical regulation, leading to emergent properties crucial for tissue development. Genetic studies revealing associations with traits like developmental dysplasia of the hip, idiopathic osteonecrosis of the femoral head, and facial morphology underscore the complex interplay of multiple genes and their products in shaping anatomical structures[9]. Dysregulation within these interconnected molecular networks, potentially stemming from identified genetic variants, can lead to developmental abnormalities. Understanding these integrated mechanisms is key to identifying points of vulnerability and potential therapeutic targets for conditions affecting complex structures.
Population Studies
Section titled “Population Studies”Understanding the population-level characteristics and determinants of the abnormality of the dentition relies on diverse epidemiological and genetic studies. These investigations leverage large cohorts, advanced genomic techniques, and cross-population comparisons to identify prevalence patterns, genetic underpinnings, and environmental influences. Methodological rigor, including careful study design and consideration of population stratification, is crucial for drawing valid conclusions about complex traits.
Large-Scale Genomic and Longitudinal Studies
Section titled “Large-Scale Genomic and Longitudinal Studies”Large-scale cohort studies and biobank initiatives are instrumental in uncovering the genetic architecture of complex traits. Genome-wide association studies (GWAS) conducted within major population cohorts, such as those contributing to meta-analyses for traits like hip bone geometry or refractive error, leverage vast sample sizes to identify common genetic variants associated with specific phenotypes[5]. These studies often involve hundreds of thousands of individuals, allowing for the detection of loci with small effect sizes and providing insights into the polygenic nature of traits. Biobank studies, like those utilizing data from cohorts such as the UK Biobank, enable longitudinal analyses to observe temporal patterns and gene-environment interactions, which are crucial for understanding the progression and etiology of various population health outcomes [12].
Meta-analyses of GWAS data combine results from multiple cohorts, significantly increasing statistical power to detect novel susceptibility loci that might be missed in individual studies. For instance, meta-analyses have identified genetic variants for hip bone geometry and multiple new susceptibility loci for refractive error and myopia, demonstrating the power of aggregating data across diverse populations[5]. These collaborative efforts, often involving numerous research institutions globally, allow for robust identification of genetic factors and provide a comprehensive view of the genetic landscape underlying complex traits [5].
Cross-Population and Ancestry-Specific Analyses
Section titled “Cross-Population and Ancestry-Specific Analyses”Population studies frequently highlight significant cross-population and ancestry-specific differences in the prevalence and genetic architecture of various traits. Research has explored genetic variants in diverse populations, including South Asian, Korean, Japanese, and African-admixed cohorts, revealing population-specific effects and ancestry-specific loci for traits such as skin pigmentation, idiopathic osteonecrosis of the femoral head, and facial morphology[1]. These studies are critical for understanding how genetic predispositions and environmental factors interact within distinct ethnic and geographic groups, contributing to variations in trait expression.
Comparisons across different ancestries help to refine the understanding of genetic associations, as allele frequencies and linkage disequilibrium patterns can vary substantially between populations [10]. For example, multiancestry cohorts have been used to identify susceptibility loci for refractive error, demonstrating the utility of incorporating diverse genetic backgrounds to enhance the discovery of generalizable and population-specific genetic factors [10]. Such comparisons are also essential for assessing the generalizability of findings from predominantly European-ancestry cohorts to other global populations.
Epidemiological Methodologies and Prevalence Insights
Section titled “Epidemiological Methodologies and Prevalence Insights”Epidemiological studies employ various methodologies to ascertain prevalence patterns and incidence rates of complex traits within populations. These investigations often account for demographic factors and socioeconomic correlates to understand their influence on health outcomes. For genetic studies, careful adjustment for population stratification is a critical methodological consideration, preventing spurious associations due to differences in ancestry between study participants [3]. Researchers often include covariates like county of birth or apply methods like LD score regression to account for such stratification and cryptic relatedness within samples[3].
The design of these studies, ranging from large prospective cohorts to extensive case-control studies, ensures representativeness and allows for the generalizability of findings to broader populations. Rigorous methodologies, including robust statistical analyses and large sample sizes, are paramount for identifying reliable epidemiological associations and genetic variants that contribute to complex traits. Ethical considerations, such as obtaining informed consent from all participants and securing approval from local medical ethics committees, are fundamental to the conduct of these large-scale population studies [10].
Frequently Asked Questions About Abnormality Of The Dentition
Section titled “Frequently Asked Questions About Abnormality Of The Dentition”These questions address the most important and specific aspects of abnormality of the dentition based on current genetic research.
1. Will my kids definitely get my crooked teeth?
Section titled “1. Will my kids definitely get my crooked teeth?”Not necessarily, but there’s a higher chance. Genetic predispositions play a significant role in how teeth develop and align, and many conditions can run in families. However, environmental factors like early habits or injuries also contribute, so it’s not a guarantee. Good dental care from an early age can help manage any inherited tendencies.
2. My sibling has perfect teeth, so why are mine so bad?
Section titled “2. My sibling has perfect teeth, so why are mine so bad?”It’s common to see differences even within families. While genetics play a big role in tooth development, the specific combination of genes you inherit can vary from your sibling’s. Plus, individual environmental factors like diet, habits, or even minor trauma during development can also contribute to how your teeth turn out.
3. Can what I eat as a kid really mess up my adult teeth?
Section titled “3. Can what I eat as a kid really mess up my adult teeth?”Yes, absolutely. Your diet and nutrition during critical stages of tooth development can significantly influence their structure and health. Nutritional deficiencies, for example, can disrupt normal formation. These environmental factors interact with your genetic makeup, impacting how your teeth ultimately form and emerge.
4. Does my family’s background affect my risk for teeth problems?
Section titled “4. Does my family’s background affect my risk for teeth problems?”Yes, your ancestry can influence your dental health. Genetic architecture, including how common certain genetic variations are, differs across populations. This means that genetic findings from one group may not directly apply to another, highlighting the importance of diverse research to understand risks specific to your background.
5. Can having crooked teeth cause other problems besides just looks?
Section titled “5. Can having crooked teeth cause other problems besides just looks?”Yes, definitely. Beyond aesthetics, abnormalities can make it harder to chew properly, affect how you speak, and even increase your risk for cavities, gum disease, and jaw joint issues. Early diagnosis and treatment are important to prevent these complications and support your overall oral health.
6. Is a DNA test useful to know about my specific teeth issues?
Section titled “6. Is a DNA test useful to know about my specific teeth issues?”While genetic factors are known to influence tooth development, the full picture for complex dental abnormalities is still being researched. Current DNA tests might not provide a complete or precise prediction for your specific condition. Many genes and environmental factors are involved, and there are still significant knowledge gaps.
7. Can good oral habits overcome my family’s history of bad teeth?
Section titled “7. Can good oral habits overcome my family’s history of bad teeth?”Yes, good habits can make a big difference! While you might have a genetic predisposition for certain dental issues, proactive measures like excellent oral hygiene, a healthy diet, and regular dental visits can significantly mitigate those risks. It’s all about the interplay between your genes and your environment.
8. Should I worry if my kid’s baby teeth look a little abnormal?
Section titled “8. Should I worry if my kid’s baby teeth look a little abnormal?”It’s always a good idea to have any concerns checked by a dentist. Abnormalities can affect both baby and permanent teeth. Early diagnosis and intervention are crucial for managing these conditions, as issues in primary teeth can sometimes indicate potential problems for the permanent dentition.
9. Does having a “weird” smile really affect how I feel about myself?
Section titled “9. Does having a “weird” smile really affect how I feel about myself?”Unfortunately, yes, it can. The appearance of your teeth and smile plays a significant role in self-esteem, social interactions, and overall psychological well-being. Visible dental irregularities can lead to self-consciousness or anxiety, impacting your quality of life, which is why treatment often has significant benefits.
10. Why don’t dentists always know the exact reason for my unique tooth problem?
Section titled “10. Why don’t dentists always know the exact reason for my unique tooth problem?”The development of teeth is incredibly complex, involving many genes and environmental factors interacting in intricate ways. Because there’s such a wide spectrum of abnormalities, and each might have a slightly different genetic cause, it can be challenging to pinpoint one single reason. Research is ongoing to better understand these complexities.
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
Section titled “References”[1] Stokowski RP et al. “A genomewide association study of skin pigmentation in a South Asian population.” Am J Hum Genet, December 2007.
[2] Lee, MK et al. “Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.”PLoS One, 2016.
[3] Hammerschlag AR et al. “Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.” Nat Genet, June 2017.
[4] Chen, J. et al. “Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes.” Nicotine & Tobacco Research, PMID: 31294817, July 2019.
[5] Hsu YH et al. “Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry.”J Bone Miner Res, March 2019.
[6] Lee MK et al. “Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.”PLoS One, April 2017.
[7] Solouki AM et al. “A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14.”Nat Genet, September 2010.
[8] Wu Y et al. “Genome-wide association study of medication-use and associated disease in the UK Biobank.”Nat Commun, April 2019.
[9] Hatzikotoulas, K et al. “Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5.” Commun Biol, 2018.
[10] Verhoeven VJ et al. “Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.”Nat Genet, February 2013.
[11] Stambolian D et al. “Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error.” Hum Mol Genet, 2013, Vol. 22, No. 13.
[12] Zengini E et al. “Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.”Nat Genet, April 2018.