Molar Incisor Hypomineralization
Molar Incisor Hypomineralization (MIH) is a common developmental dental defect characterized by demarcated opacities in the enamel of one or more permanent first molars, often accompanied by similar defects in permanent incisors. These opacities can vary in color from white to yellow or brown and can lead to significant enamel breakdown, especially in severe cases. MIH is a global health concern, affecting a substantial percentage of children worldwide, and is a major focus in pediatric dentistry due to its varied clinical manifestations and implications for oral health.
Biological Basis
Section titled “Biological Basis”The precise etiology of MIH is multifactorial, involving a complex interplay of systemic and genetic factors that disrupt amelogenesis, the process of enamel formation, during the early stages of tooth development. While specific genetic markers directly linked to MIH are still under active investigation, research into general tooth development and susceptibility to dental conditions provides insights into potential genetic contributions. For instance, genome-wide association studies (GWAS) on dental caries have highlighted genes involved in tooth structure and morphology.
Genetic variations within or near genes like BCOR (BCL6 corepressor) have been explored in relation to dental abnormalities. Null mutations in BCOR are known to cause severe dental abnormalities, suggesting that genetic variations in this gene could influence tooth development and, consequently, modify susceptibility to various dental conditions.[1] Another gene, INHBA (inhibin, beta A), a member of the TGFβ superfamily, is crucial for early tooth bud formation. Its expression in mesenchymal cells is essential for proper tooth development, and disruptions, as observed in mouse knockouts, can lead to abnormal tooth eruption of incisors and mandibular molars.[1] These findings suggest that genetic predispositions affecting the quality and development of enamel likely contribute to the manifestation of MIH.
Clinical Relevance
Section titled “Clinical Relevance”Clinically, MIH poses significant challenges for both patients and dental professionals. The hypomineralized enamel is often porous, weaker, and more susceptible to rapid decay, even with diligent oral hygiene practices. Individuals with MIH frequently experience heightened dental hypersensitivity to thermal, chemical, and mechanical stimuli, leading to pain and discomfort during eating, drinking, and routine brushing. This sensitivity can make daily oral care difficult and impact a child’s quality of life. Restorative treatments for MIH-affected teeth are often complex due to the compromised enamel’s poor bond strength with dental materials and the challenges of managing patient discomfort and cooperation. Early diagnosis and intervention are critical to prevent extensive tooth destruction, manage pain, and reduce the need for more invasive and costly dental procedures.
Social Importance
Section titled “Social Importance”The prevalence of MIH underscores its significant social importance. Beyond the clinical challenges, MIH can affect a child’s self-esteem and social interactions, particularly when permanent incisors are affected, leading to aesthetic concerns. The chronic pain and sensitivity associated with MIH can also impact school attendance, concentration, and overall well-being. From a public health perspective, the high incidence of MIH represents a substantial burden on dental healthcare systems. The need for frequent check-ups, specialized treatments, and ongoing management contributes to increased healthcare costs for families and providers. A deeper understanding of the underlying causes, including genetic and environmental factors, is crucial for developing effective prevention strategies and improving long-term oral health outcomes for affected individuals.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Research into molar incisor hypomineralization (MIH) is subject to several methodological and statistical limitations that can impact the reliability and generalizability of findings. Studies often contend with sample sizes that are comparatively small for genome-wide association study (GWAS) standards, which consequently leads to low statistical power and increases the possibility of false-positive findings, particularly for infrequent genetic variants.[2] This challenge is sometimes compounded by cohort bias, where selective participation can distort genetic associations and downstream analyses, potentially leading to skewed results.[3] Furthermore, issues such as cryptic relatedness, model misspecification, or the polygenic nature of a trait can contribute to genomic inflation, requiring caution when interpreting p-values and strict thresholds for statistical significance.[1] Replication of findings is crucial but often hindered by challenges in achieving phenotypic homogeneity across different cohorts, even when sample sizes are larger.[4] Regional and ethnic differences between cohorts may alter genetic effects, precluding successful replication, especially if variants have low minor allele frequencies (MAF) in particular ancestral groups, thereby limiting the power to observe effects in diverse populations.[4] The use of the same dataset for discovery and selection of genetic instruments can also impinge on results, though this impact may be minimal with sufficiently large GWAS sample sizes.[5]
Phenotypic Measurement and Generalizability
Section titled “Phenotypic Measurement and Generalizability”Accurate phenotyping is a significant challenge in MIH research, as imperfect phenotypic measurement directly affects the power of association tests for both common and rare variants.[6] The phenotype itself can be “noisy” due to confounding factors, hidden sources of variability, or determinants beyond the primary biological function being studied, which limits the interpretability of genetic variants impacting the trait.[6] Ensuring standardized procedures for generating and harmonizing phenotype data is essential to mitigate these issues.[2] Generalizability of findings across diverse populations is another critical limitation. Many studies may primarily include individuals of European ancestry for imputation and analysis, which limits the direct applicability of findings to other ancestral groups.[1] Despite efforts to mitigate biases from population structure through stratified analyses and adjustment for principal components, it remains plausible that population substructure could influence findings.[7] Differences in causal variants, haplotype structure, or gene-environment interactions between populations can lead to variations in genetic effects or even a lack of generalization for variants found in one population to another.[8]
Incomplete Genetic Architecture and Environmental Factors
Section titled “Incomplete Genetic Architecture and Environmental Factors”The current understanding of MIH’s genetic architecture is incomplete, with a notable gap between heritability estimates from twin- and family-based studies and the proportion of variance explained by identified common variants in GWAS.[6] This “missing heritability” suggests that other sources of genetic variation, including rare variants, or unconsidered environmental factors, contribute significantly to the trait.[6] While large sample sizes are crucial for detecting rare variant associations, studies may still be underpowered to fully capture their impact.[6] Environmental and gene-environment confounders also represent a substantial knowledge gap. Heterogeneity in environmental exposures between populations, such as dietary factors or other external influences, can interact with genetic predispositions and alter genetic effects, making it difficult to isolate the precise genetic contributions to MIH.[8] Consequently, despite identifying significant associations, known genetic variants often account for only a small proportion of the observed phenotypic variance, indicating that many susceptibility variants for MIH, particularly those with smaller effect sizes or those influenced by complex environmental interactions, are yet to be discovered.[4]
Variants
Section titled “Variants”Genetic variations play a crucial role in determining an individual’s susceptibility to molar incisor hypomineralization (MIH) by influencing diverse biological pathways essential for proper tooth development and enamel formation. Variants in genes involved in cellular metabolism, structural integrity, DNA maintenance, and gene regulation can perturb the intricate process of amelogenesis, leading to defects in enamel quality. Genome-wide association studies (GWAS) have been instrumental in identifying genetic loci associated with various dental traits, including those that may overlap with MIH pathogenesis.[1], [9] The region near PPARGC1A (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha) and DHX15 (DExH-Box Helicase 15) contains the variant rs17650401 , which may impact the energetic and metabolic processes critical for ameloblast function. PPARGC1A is a master regulator of mitochondrial biogenesis and oxidative metabolism, essential for the high energy demands of ameloblasts during enamel matrix formation and mineralization. Disruption in these energy pathways, potentially influenced by rs17650401 , could compromise the ameloblasts’ ability to produce and process enamel proteins, leading to hypomineralization. Similarly, DHX15, an RNA helicase, is involved in pre-mRNA splicing, ensuring the correct expression of genes vital for cell differentiation and function.[9] Altered splicing due to variants could affect the production of key proteins required for normal enamel development, thus contributing to MIH.
Other variants, such as rs13058467 near TTLL12 (Tubulin Tyrosine Ligase Like 12) and rs13288553 associated with RMI1 (RecQ-Mediated Genome Instability Protein 1) and SLC28A3 (Solute Carrier Family 28 Member 3), highlight the importance of cellular structure, DNA integrity, and nutrient transport in enamel health. TTLL12 plays a role in modifying tubulin, which is fundamental for microtubule dynamics, cellular transport, and the highly organized architecture of ameloblasts necessary for efficient enamel matrix secretion.[1] Variances affecting TTLL12 could therefore disrupt ameloblast function and contribute to MIH. Furthermore, RMI1 is involved in DNA repair pathways, crucial for maintaining genomic stability in rapidly dividing and differentiating ameloblasts, while SLC28A3is a nucleoside transporter, ensuring the supply of building blocks for DNA and RNA synthesis. Perturbations in these processes, influenced byrs13288553 , could lead to ameloblast dysfunction or premature cell death, ultimately affecting enamel quality and manifesting as MIH.
The genetic landscape of MIH also includes regions near ion channels and non-coding RNAs, exemplified by rs4811117 linked to KCNG1(Potassium Voltage-Gated Channel Modifier Subfamily G Member 1) andRPSAP1 (Ribosomal Protein S4 Pseudogene 1), and rs1126179 near LINC00922 (Long Intergenic Non-Protein Coding RNA 922) and RNA5SP428 (RNA, 5S Ribosomal Pseudogene 428). KCNG1encodes a potassium channel subunit, and ion channels are vital for regulating cellular signaling, pH, and calcium transport within ameloblasts—processes indispensable for the precise maturation of enamel. Variations inKCNG1 may therefore impair the delicate ionic balance required for proper enamel mineralization. Long non-coding RNAs like LINC00922 and pseudogenes such as RPSAP1 and RNA5SP428 can exert regulatory control over gene expression, influencing developmental programs and cellular differentiation.[9] Alterations in these regulatory elements, potentially mediated by rs4811117 and rs1126179 , could disrupt the coordinated gene expression necessary for healthy amelogenesis, contributing to the etiology of molar incisor hypomineralization.
Key Variants
Section titled “Key Variants”Causes of Molar Incisor Hypomineralization
Section titled “Causes of Molar Incisor Hypomineralization”Molar incisor hypomineralization (MIH) is a developmental disturbance affecting the enamel of permanent first molars and often permanent incisors. Its etiology is complex, involving a combination of genetic predispositions, environmental exposures, and their intricate interactions during critical stages of tooth development. Understanding these diverse causal pathways is essential for prevention and management.
Genetic Predisposition and Tooth Development
Section titled “Genetic Predisposition and Tooth Development”Genetic factors play a fundamental role in shaping tooth development and morphology, which can predispose individuals to conditions like molar incisor hypomineralization. Inherited genetic variants can influence the intricate processes of enamel formation, leading to structural weaknesses or developmental defects. Studies suggest that specific genetic factors involved in the patterning of tooth morphology during early development may affect different tooth surfaces uniquely, highlighting a genetic basis for variations in tooth structure.[1]While specific Mendelian forms directly causing molar incisor hypomineralization are not detailed in the researchs, the concept of polygenic risk, where multiple genetic variants collectively contribute to susceptibility, is broadly applicable to complex traits. The fetal genome, including variants near genes such as pro-inflammatory cytokine genes on 2q13, can represent early life genetic influences that potentially impact developmental trajectories, including those related to dental health. These genetic predispositions may also involve complex gene-gene interactions, where the combined effect of several genetic loci dictates the ultimate phenotype.[10]
Environmental and Early Life Influences
Section titled “Environmental and Early Life Influences”Environmental factors significantly contribute to the risk of molar incisor hypomineralization by influencing the delicate process of enamel maturation. Lifestyle choices, dietary habits, and exposure to various substances during critical periods of tooth development can disrupt amelogenesis, leading to hypomineralized enamel. Socioeconomic status and the living environment are also recognized as broad determinants of health, potentially influencing access to proper nutrition and healthcare, which indirectly impacts dental developmental outcomes.[1]Early life influences, particularly during gestation and infancy, are crucial determinants of dental health. Factors affecting fetal development, such as those related to gestational duration and the fetal genome, can have lasting effects on tooth structure and mineralization. While specific epigenetic mechanisms like DNA methylation or histone modifications are not explicitly detailed in the provided studies concerning molar incisor hypomineralization, these early developmental periods are known to be sensitive to environmental cues that can induce epigenetic changes, thereby altering gene expression patterns critical for proper enamel formation.[10]
Interplay of Genes and Environment
Section titled “Interplay of Genes and Environment”Molar incisor hypomineralization often arises from a complex interplay between an individual’s genetic predisposition and various environmental exposures. Genetic factors can modulate how individuals respond to environmental triggers, meaning that certain genetic variants might make an individual more sensitive or resistant to factors that disrupt enamel formation. For instance, specific genetic variations, such as those in fluoride-sensitivity genes or taste-preference genes, could influence an individual’s response to fluoride intake or dietary choices, thereby altering their susceptibility to developmental enamel defects.[1]Beyond direct genetic and environmental influences, other factors can contribute to the manifestation and severity of molar incisor hypomineralization. While the researchs does not explicitly detail specific comorbidities or medication effects pertaining to this condition, systemic health issues or early childhood medications could potentially interfere with ameloblast function during critical periods of tooth development. Furthermore, age is a factor considered in dental health research, suggesting that the duration of exposure to various factors, or the cumulative impact over time, can influence the presentation of dental conditions.[1]
Genetic Blueprint of Tooth Development and Morphology
Section titled “Genetic Blueprint of Tooth Development and Morphology”The intricate process of tooth formation and the resulting morphology are significantly influenced by a complex interplay of genetic factors. Genes play a crucial role in patterning tooth structures during development, impacting features such as the distinct characteristics of pit-and-fissure versus smooth surfaces.[11] For instance, the BCOR gene is implicated in severe dental abnormalities, with null mutations leading to significant developmental defects.[1] Studies have shown that silenced Bcor expression in dental tissues can cause defects in dentinogenesis and impede tooth root development, suggesting that genetic variations within or near this gene may alter tooth development and, consequently, modify susceptibility to various dental issues.[1] Another key gene, INHBA (inhibin, beta A), is essential for early tooth development and the proper formation of tooth buds.[1] INHBA encodes a subunit of activin and inhibin, both members of the transforming growth factor beta (TGFβ) superfamily, which is critical for various developmental processes. Genetic variations, such as the rs10486722 SNP located in the 5′ region upstream of INHBA and within the non-coding RNA INHBA-AS1, highlight potential regulatory elements influencing INHBA expression and its impact on tooth morphology.[1] These genetic underpinnings are fundamental to understanding the structural integrity and developmental health of molars and incisors.
Molecular Signaling Pathways in Odontogenesis
Section titled “Molecular Signaling Pathways in Odontogenesis”Tooth development, or odontogenesis, is orchestrated by complex molecular signaling pathways, with the TGFβ superfamily playing a pivotal role. The INHBA gene’s product, activin, is a key ligand in this pathway, interacting with specific activin receptors IIA and IIB.[1] This signaling cascade utilizes effector molecules like Smad2 to transmit signals that regulate cell proliferation, differentiation, and matrix deposition during tooth formation. The precise regulation of these molecular interactions is crucial for the normal progression of odontogenesis, from the initial tooth bud stage through to the maturation of dental tissues.
Disruptions to the activin signaling pathway can have profound consequences on tooth development. Research has demonstrated that inhibiting activin signaling, either through exogenous soluble receptors or mutations in key components like activin receptors IIA, IIB, or Smad2, leads to significant dental aberrations.[1] These findings underscore the importance of the TGFβ superfamily and activin signaling in maintaining the delicate balance required for proper tooth morphogenesis and the subsequent establishment of robust tooth structure. Such molecular pathways are critical for the formation of well-mineralized enamel and dentin.
Cellular and Tissue-Level Dynamics of Dental Formation
Section titled “Cellular and Tissue-Level Dynamics of Dental Formation”The formation of dental tissues, including enamel and dentin, relies on the precise coordination of various cell types, particularly mesenchymal cells. The expression of Inhba in mesenchymal cells is indispensable for the initiation of early tooth development and the subsequent formation of tooth buds.[1]These mesenchymal cells possess osteo-dentinogenic potential, meaning they can differentiate into cells responsible for forming bone-like and dentin tissues. The proper function and differentiation of these cells are critical for establishing the foundational structure of the tooth.
Any disruption in the cellular processes of dentinogenesis can lead to structural defects. For example, silenced Bcor expression has been shown to cause dentinogenesis defects and a delay in tooth root development.[1] These cellular-level anomalies can result in compromised dentin and root structures, affecting the overall integrity and strength of the tooth. The harmonious interaction between epithelial and mesenchymal cells, guided by signaling molecules and transcription factors, is essential for the ordered deposition of mineralized matrix that forms healthy enamel and dentin.
Pathophysiological Consequences of Developmental Disruptions
Section titled “Pathophysiological Consequences of Developmental Disruptions”Developmental processes are highly sensitive to genetic and environmental influences, and disruptions can manifest as significant dental abnormalities. When the finely tuned genetic mechanisms and molecular pathways governing tooth development are perturbed, the resulting tooth morphology and composition can be severely affected.[11] Conditions such as severe dental abnormalities, dentinogenesis defects, and disrupted tooth eruption have been observed in studies involving gene knockouts or silenced gene expression, highlighting the critical role of specific genes like BCOR and INHBA in maintaining dental health.[1] These structural and developmental aberrations can significantly compromise the resilience of teeth.
The consequences of such developmental disruptions include an altered tooth morphology and potentially weakened tooth structure, which can modify the susceptibility to various dental problems. For instance, developmental defects can lead to surfaces that are more vulnerable to external factors, regardless of other environmental exposures.[11] This increased susceptibility underscores how fundamental developmental processes, when disrupted, can predispose specific teeth, such as molars and incisors, to long-term structural and functional issues.
Clinical Relevance of Molar Incisor Hypomineralization
Section titled “Clinical Relevance of Molar Incisor Hypomineralization”Molar incisor hypomineralization (MIH) represents a significant clinical challenge in pediatric dentistry due to its impact on tooth structure and subsequent susceptibility to various oral health issues. Understanding its clinical relevance involves assessing its prognostic implications, guiding diagnostic and management strategies, and recognizing its broader associations with patient well-being.
Prognostic Implications and Disease Progression
Section titled “Prognostic Implications and Disease Progression”Molar incisor hypomineralization (MIH) is characterized by developmental defects in enamel, which can significantly influence the prognosis of affected teeth and overall oral health outcomes. Teeth with MIH, particularly molars, often exhibit compromised enamel integrity, making them highly susceptible to rapid carious breakdown, even in primary dentition.[1]The progression of dental caries, which is a multifactorial condition influenced by genetic and environmental factors, can lead to profound effects on a child’s quality of life, including chronic pain, tooth loss, difficulties with eating and sleeping, and, in severe cases, failure to thrive.[1] Therefore, identifying MIH early allows for a more accurate prediction of future oral health challenges and the potential for extensive restorative needs throughout a patient’s life, necessitating proactive and consistent intervention strategies to mitigate these long-term implications.
Diagnostic Utility and Risk-Stratified Management
Section titled “Diagnostic Utility and Risk-Stratified Management”The recognition of MIH is crucial for effective diagnostic utility and the implementation of risk-stratified management approaches. Clinicians can use the presence and severity of MIH as a key indicator for heightened risk assessment, enabling the identification of individuals who require more intensive preventive and restorative care. Since cariogenesis is influenced by a complex interplay of genetic factors, environmental exposures, and oral hygiene practices, understanding the underlying enamel defect in MIH allows for personalized treatment selection beyond conventional caries management.[1]This includes tailored monitoring strategies, such as more frequent recalls, application of desensitizing agents, fluoride varnishes, and early placement of protective restorations or sealants, to prevent the rapid progression of decay that is often seen in hypomineralized teeth. Such targeted interventions can help reduce the burden of disease, which is known to vary across socioeconomic and ethnic strata, and improve oral health outcomes.[1]
Associated Complications and Holistic Patient Care
Section titled “Associated Complications and Holistic Patient Care”MIH is associated with several clinical complications that extend beyond simple carious lesions, impacting the overall well-being and requiring a holistic approach to patient care. The compromised enamel structure often leads to increased tooth sensitivity, which can affect dietary habits and compliance with oral hygiene practices, further exacerbating the risk of caries and pain. The profound effects of childhood dental caries, which hypomineralized teeth are prone to, can manifest as substandard school performance, poor social relationships, and decreased success later in life.[1]Consequently, managing MIH requires addressing these broader implications, integrating pain management, dietary counseling, and psychological support alongside dental treatments to improve the child’s quality of life and prevent long-term negative impacts on their physical and social development.
Frequently Asked Questions About Molar Incisor Hypomineralization
Section titled “Frequently Asked Questions About Molar Incisor Hypomineralization”These questions address the most important and specific aspects of molar incisor hypomineralization based on current genetic research.
1. Why do my child’s teeth hurt so much with cold drinks?
Section titled “1. Why do my child’s teeth hurt so much with cold drinks?”Your child’s teeth affected by MIH have enamel that is often porous and weaker than normal. This compromised enamel doesn’t provide adequate protection to the sensitive inner layers of the tooth, leading to heightened hypersensitivity. This pain can be easily triggered by thermal stimuli like cold drinks.
2. Will my other children also get these tooth spots?
Section titled “2. Will my other children also get these tooth spots?”It’s possible, as MIH has a strong genetic component, meaning a predisposition can run in families. While not every child will be affected, genetic variations in genes like BCOR or INHBA that influence tooth development can increase susceptibility. However, environmental factors also play a role, so it’s not a guarantee.
3. Why are my child’s cavities so hard for the dentist to fix?
Section titled “3. Why are my child’s cavities so hard for the dentist to fix?”Teeth affected by MIH have compromised enamel that is inherently weaker and more porous, making it challenging for dental materials to bond effectively. This poor bond strength means restorations might not last as long or be as stable. Managing your child’s discomfort and cooperation during treatment can also add to the complexity.
4. Do these tooth spots affect my child’s self-esteem?
Section titled “4. Do these tooth spots affect my child’s self-esteem?”Yes, they can, especially if the permanent incisors are affected, as the visible spots can lead to aesthetic concerns. Beyond appearance, chronic pain and sensitivity from MIH can impact your child’s daily life, affecting school concentration and social interactions, which can definitely influence their overall well-being and confidence.
5. Why do my child’s teeth decay so fast despite good brushing?
Section titled “5. Why do my child’s teeth decay so fast despite good brushing?”The enamel affected by MIH is intrinsically weaker and more porous than healthy enamel, making it highly susceptible to rapid decay. Even with diligent oral hygiene, these teeth are more vulnerable to acid attacks and breakdown. This means they need extra care and early professional intervention to protect them effectively.
6. Is it true that some people just have naturally weaker tooth enamel?
Section titled “6. Is it true that some people just have naturally weaker tooth enamel?”Yes, it is true. MIH is a developmental defect where the enamel forms with structural weaknesses due to disruptions in the amelogenesis process. This can be influenced by genetic predispositions affecting genes like INHBA that are crucial for proper tooth development, leading to naturally weaker and more porous enamel.
7. My sibling has perfect teeth, why are mine so problematic?
Section titled “7. My sibling has perfect teeth, why are mine so problematic?”Even within the same family, genetic expression and environmental influences can vary significantly. While a genetic predisposition might exist for MIH, the specific manifestation can differ greatly. This “missing heritability” suggests other genetic variations or unique environmental factors contribute to individual differences.
8. Does my family background mean I’m more prone to this tooth issue?
Section titled “8. Does my family background mean I’m more prone to this tooth issue?”Yes, your family background, especially your genetic ancestry, can influence your susceptibility to MIH. Genetic variations associated with tooth development can differ across populations. While much research has focused on European ancestries, it’s plausible that your specific background could carry different risk factors.
9. Can I prevent my child from getting these tooth problems?
Section titled “9. Can I prevent my child from getting these tooth problems?”MIH is a developmental defect that occurs during tooth formation, so preventing the initial enamel defect itself is challenging as it’s often due to systemic and genetic factors. However, early diagnosis and proactive dental care can prevent extensive tooth destruction, manage pain, and reduce the need for more invasive treatments later on.
10. Why does my dentist stress “early diagnosis” for my child’s teeth?
Section titled “10. Why does my dentist stress “early diagnosis” for my child’s teeth?”Early diagnosis is crucial because MIH-affected teeth are prone to rapid decay and severe pain. Identifying it early allows for timely intervention to strengthen the enamel, manage sensitivity, and apply protective measures. This prevents extensive tooth destruction and avoids more complex, costly, and painful procedures in the future.
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] Zeng, Z., et al. “Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition.” J Dent Res, vol. 92, no. 5, 2013, pp. 432-437. PMID: 23470693.
[2] Homann, J. et al. “Genome-Wide Association Study of Alzheimer’s Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery Dataset.”Front Aging Neurosci, vol. 14, 2022. PMID: 35386118.
[3] Schoeler, T. et al. “Participation bias in the UK Biobank distorts genetic associations and downstream analyses.” Nat Hum Behav, vol. 7, no. 5, 2023. PMID: 37106081.
[4] Smith, SB. et al. “Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.” Pain, vol. 159, no. 12, 2018. PMID: 30431558.
[5] Yuan, F. et al. “Blood metabolic biomarkers and colorectal cancer risk: results from large prospective cohort and Mendelian randomisation analyses.”Br J Cancer, vol. 130, no. 8, 2024. PMID: 40307439.
[6] Pillalamarri, V. et al. “Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number.”HGG Adv, vol. 4, no. 3, 2023. PMID: 36311265.
[7] Chong, M. et al. “GWAS and ExWAS of blood Mitochondrial DNA copy number identifies 71 loci and highlights a potential causal role in dementia.”Elife, vol. 11, 2022. PMID: 35023831.
[8] Raffield, LM. et al. “Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation?”Hum Mol Genet, vol. 26, no. 11, 2017. PMID: 28334935.
[9] Zeng, Z. et al. “Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.” Caries Res, vol. 49, no. 1, 2015, pp. 24-30.
[10] Liu, X. et al. “Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.”Nat Commun, vol. 10, no. 1, 2019, p. 3968.
[11] Zeng, Z. et al. “Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.” Caries Res, vol. 48, no. 4, 2014. PMID: 24556642.