Cataract
Cataract is a common eye condition characterized by the progressive clouding of the eye’s natural lens, which can lead to blurred vision, difficulty seeing at night, and eventual vision loss[1]. While it can manifest as a developmental disorder in younger individuals, known as congenital or pediatric cataracts, it is most frequently observed as an age-related disease[1]. Globally, cataract is the leading cause of blindness, and in the United States, it is the primary cause of vision loss[2].
The biological basis of cataract involves the opacification of the crystalline lens. Genetic factors play a significant role in an individual’s susceptibility to cataract, with twin and family studies estimating heritability between 35% and 58%[1]. Research has identified multiple genetic loci linked to cataract as an independent trait, and genes implicated in childhood cataract are also considered plausible candidates for age-related forms[2]. Recent large-scale genetic studies, including multiethnic Genome-Wide Association Studies (GWAS), have uncovered new risk loci and demonstrated sex-specific genetic effects [1]. For example, a meta-analysis identified 54 lead single nucleotide polymorphisms (SNPs) associated with cataract[1]. The development of tools like Polygenic Risk Scores (PRS) shows promise in improving cataract prediction, particularly in diverse populations[3].
Clinically, cataract affects a substantial portion of the population; estimates indicate that 17.2% of Americans aged 40 and older have cataract in at least one eye, with 5.1% having undergone cataract surgery[2]. The condition has considerable implications for healthcare, accounting for approximately 60% of Medicare costs related to vision [2]. Beyond vision impairment, cataract has been associated with an increased risk of falls and, potentially, increased mortality[2]. Women tend to have a slightly higher risk of developing cataracts and undergoing cataract surgery than men[2].
From a societal perspective, the growing global life expectancy suggests a dramatic increase in the number of cataract cases and surgeries in the coming years[2]. This trend underscores the urgent need for effective primary prevention strategies to mitigate the public health and economic burden of this widespread condition [2].
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of cataract susceptibility is a complex endeavor, and current research should be interpreted within the context of several inherent limitations. These challenges span from how the phenotype is defined to the generalizability of findings across diverse populations and the complete elucidation of underlying biological mechanisms.
Challenges in Phenotype Definition and Measurement
Section titled “Challenges in Phenotype Definition and Measurement”A significant limitation in cataract research stems from the variability in how the cataract phenotype is assessed across different study cohorts. Some studies rely on electronic health records (EHRs) and International Classification of Disease (ICD) codes, while others depend on self-reported data. This heterogeneity in phenotyping methods can lead to potential misclassification of cases and controls, which may affect the accuracy of genetic association signals and the overall interpretability of findings[1]. Furthermore, studies frequently focus on cataract surgery as the primary phenotype, which means individuals with early-stage cataract who have not yet undergone surgery might be inadvertently included in control groups. The inherent limitations of EHR data for specific ophthalmic conditions, such as the often-limited or absent coded information, also necessitate the development of sophisticated phenotyping strategies, highlighting the challenges in obtaining precise and consistent cataract definitions[1].
Generalizability Across Diverse Populations
Section titled “Generalizability Across Diverse Populations”While recent large-scale genetic studies have made efforts to include multiethnic cohorts, a comprehensive understanding of how identified genetic loci contribute to cataract risk across all diverse ethnic backgrounds remains an ongoing challenge. Much of the historical genetic research has predominantly focused on populations of European descent, which limits the direct transferability of findings to other ancestral groups and potentially overlooks population-specific genetic variants or effect modifications. The varying genetic architectures and environmental exposures present across different ancestral groups mean that findings from one population may not be universally applicable, leading to potential disparities in risk prediction and the development of targeted prevention or treatment strategies[1]. This underscores the critical need for continued research in a broader spectrum of global populations to ensure equitable health outcomes.
Incomplete Understanding of Genetic Architecture and Environmental Factors
Section titled “Incomplete Understanding of Genetic Architecture and Environmental Factors”Despite significant advances in identifying genetic loci associated with cataract, a comprehensive understanding of the complex interplay between the human genome and cataract development, including the underlying molecular mechanisms, is still emerging. The full extent of missing heritability for cataract remains to be elucidated, indicating that a substantial portion of genetic variance influencing the trait is yet to be discovered. Furthermore, the precise contribution of environmental factors and complex gene-environment interactions to cataract susceptibility is not yet fully characterized, representing a considerable knowledge gap that limits a holistic view of the disease etiology[1]. While replication efforts are crucial for validating findings, the consistent independent replication of all identified loci across diverse cohorts remains an ongoing challenge, with some previously reported genetic associations for cataract lacking independent validation[1]. Bridging these remaining knowledge gaps is essential to unraveling the intricate human genome-phenome relationships, developing more accurate predictive models, and ultimately advancing primary prevention strategies and targeted therapies for cataract.
Variants
Section titled “Variants”Genetic variations play a crucial role in determining an individual’s susceptibility to cataract, a common eye condition characterized by the clouding of the eye’s natural lens. These variations, known as single nucleotide polymorphisms (SNPs), can occur within or near genes involved in lens development, maintenance, and cellular function, influencing pathways critical for maintaining lens transparency.
Variants within the SLC24A3 gene, such as rs4814857 and rs6046142 , are particularly notable for their association with lens disorders. SLC24A3, or Solute Carrier Family 24 Member 3, encodes a protein thought to be involved in retinal diseases, suggesting a broader role in ocular health. This clouding of the normally transparent lens is the leading cause of blindness globally and the primary cause of vision loss in the United States [2]. Related terminology includes “pseudophakia” or “aphakia,” which refer to the status of having undergone previous cataract surgery, indicating a history of the condition[2]. The term “cataract extraction” is used to describe the surgical procedure performed to remove the opaque lens, a common intervention given the condition’s high prevalence.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs17172647 | ZNF619P1 - HMGN1P19 | cataract |
| rs4814857 rs6046142 | SLC24A3 | cataract eye disease |
| rs150648223 rs79721202 rs148920596 | SMIM38 - MYEOV | cataract retinal layer thickness |
| rs9895741 rs112364254 rs71373084 | NPLOC4 | cataract amblyopia |
| rs12593 | COQ8A | cataract neutrophil count lymphocyte count monocyte count leukocyte quantity |
| rs10663094 rs9842371 rs113439088 | SOX2-OT | cataract corneal topography |
| rs9038 | SEPTIN9 | Hypermetropia Hypermetropia, Myopia cataract corneal resistance factor refractive error |
| rs10500355 rs7184522 | RBFOX1 | Abnormality of refraction Myopia cataract refractive error, age at onset, Myopia |
| rs2274224 | PLCE1, PLCE1-AS1 | body fat percentage brain connectivity attribute calcium measurement brain physiology trait cataract |
| rs73015318 | QKI | cataract |
Classification and Subtypes
Section titled “Classification and Subtypes”Cataracts are broadly classified based on their etiology and age of onset. They can manifest as a developmental disorder in younger patients, known as congenital or pediatric cataracts, but more commonly present as a disease associated with aging, termed age-related cataract[1]. Within age-related cataracts, specific subtypes are recognized based on the location of opacification within the lens: nuclear cataract, cortical cataract, and posterior subcapsular (PSC) cataract[2]. These classifications are crucial for understanding the distinct clinical presentations and potential genetic or environmental risk factors associated with each type, with familial aggregation studies supporting a significant role for genetic factors in cataract susceptibility.
Diagnostic and Measurement Approaches
Section titled “Diagnostic and Measurement Approaches”The diagnosis and measurement of cataract involve both clinical criteria and research-specific methodologies. Clinically, cataract can be graded using standardized systems like the Lens Opacities Classification System III (LOCS III) or the Wisconsin grade, which allow for a dimensional assessment of severity, often through slit-lamp examination or lens photography[4]. For research purposes, cataract status can be defined categorically (presence or absence) or using specific thresholds from these grading systems, such as LOCS III grade 4 or higher, or Wisconsin grade 3 or higher[4]. Operational definitions for case identification in large studies include the presence of International Classification of Disease (ICD9 or ICD10) diagnosis codes, evidence of cataract extraction surgery, or multiple diagnostic entries in electronic health records, sometimes supplemented by natural language processing of clinical notes[1]. Controls are typically defined as individuals of an appropriate age range (e.g., 50 years or older) with no diagnostic codes for cataract or history of surgery[2].
Signs and Symptoms
Section titled “Signs and Symptoms”Cataract, characterized by the opacification of the crystalline lens, leads to a progressive loss of vision and is a primary cause of visual impairment globally and in the United States . While often associated with aging, it can also manifest as a developmental disorder[1]. Its etiology is complex, involving a combination of genetic predispositions, environmental exposures, and various physiological factors.
Genetic Susceptibility
Section titled “Genetic Susceptibility”The development of cataract is significantly influenced by genetic factors, with twin and family studies indicating a heritability ranging from 35% to 58%[1], [5]. Genes implicated in childhood cataract are hypothesized to be plausible candidates for age-related cataract[6]. Specific genetic variants contribute to different cataract types; for instance, evidence points to major genes for cortical cataract[7]. Several candidate genes, including galactokinase, apolipoprotein E, glutathione S-transferase, N-acetyltransferase 2, and EPHA2, have been associated with cataract susceptibility[2].
Beyond single gene effects, the cumulative impact of multiple genetic variations contributes to an individual’s overall risk. Polygenic risk scores, which aggregate the effects of numerous genetic loci, have been shown to improve cataract prediction, particularly in diverse populations[3]. Genome-wide association studies (GWAS) have identified novel risk loci and revealed sex-specific genetic effects on cataract susceptibility across various ethnic groups[1], [8]. Furthermore, common variants in genes like SOX-2, known for their role in congenital cataract, also contribute to age-related nuclear cataract, and specific mutations, such as L45P and Y46D, can directly lead to the aggregation of lens proteins like γC-crystallin, causing opacification[4], [9].
Environmental and Lifestyle Factors
Section titled “Environmental and Lifestyle Factors”Environmental exposures and lifestyle choices play a significant role in cataract formation. Prolonged exposure to sunlight, particularly ultraviolet B (UVB) radiation, is a recognized risk factor for lens opacities[10], [11]. Lifestyle habits such as cigarette smoking are also strongly implicated, contributing to the familial aggregation of cataract, with studies demonstrating that smoking cessation can lead to a reduced risk[12], [13].
Interactions Between Genes and Environment
Section titled “Interactions Between Genes and Environment”Cataract development is often a result of intricate interactions between an individual’s genetic makeup and their surrounding environment. Research efforts are dedicated to unraveling these gene-environment interactions, recognizing that genetic predispositions can be modulated or triggered by external factors[2]. For example, the combined influence of polygenic effects and cigarette smoking accounts for a portion of the observed familial clustering of cataract[12]. Additionally, specific obesity-related genes, such as FTO, have been linked to nuclear cataract in certain Asian populations, even though obesity itself might not be directly associated with that particular cataract subtype[14].
Age, Comorbidities, and Developmental Influences
Section titled “Age, Comorbidities, and Developmental Influences”Age is the most prominent risk factor for cataract, with the condition predominantly manifesting as a disease of aging[1]. Beyond chronological age, various comorbidities and medications can contribute to or accelerate lens opacification. Systemic conditions such as a higher body mass index (BMI) increase the risk for cortical and posterior subcapsular cataract, and type 2 diabetes is associated with increased susceptibility, with specific single-nucleotide polymorphisms linked to this comorbidity[2], [15]. Certain medications, particularly corticosteroids, are also known to promote cataract formation[16].
Cataract can also present as a developmental disorder, known as congenital or pediatric cataract, emphasizing the role of early life factors and genetic mutations in lens development[1]. An example includes fructose intolerance, which has been associated with congenital cataract[17]. Epigenetic mechanisms, such as N6-methyladenosine (m6A) modifications regulated by METTL3, have been observed to modulate the proliferation and apoptosis of lens epithelial cells in diabetic cataract, highlighting the influence of regulatory pathways on gene expression[18]. Furthermore, polymorphisms in DNA repair genes, such as the 8-oxoguanine DNA glycosylase gene Ser326Cys, are associated with age-related cataract, underscoring the importance of maintaining genomic integrity in lens health[19].
Biological Background
Section titled “Biological Background”Cataract is a prevalent ocular condition characterized by the opacification of the crystalline lens, a critical component of the eye’s optical system[3]. This progressive clouding of the lens leads to visual impairment, ranging from blurry vision and glare to complete blindness, making it a leading cause of vision loss globally[3]. While cataracts can manifest as a developmental disorder in younger individuals, known as congenital or pediatric cataracts, they are more commonly a disease associated with aging[1]. Understanding the intricate biological mechanisms underlying cataract formation is crucial for developing effective prevention and therapeutic strategies beyond surgical intervention.
The Crystalline Lens: Structure and Normal Function
Section titled “The Crystalline Lens: Structure and Normal Function”The crystalline lens is a transparent, biconvex structure located behind the iris, essential for converging light and focusing clear images onto the retina [3]. Its remarkable clarity is maintained by a highly ordered arrangement of specialized elongated cells and a high concentration of soluble proteins called crystallins, which are precisely packed to minimize light scattering [3]. The lens is an avascular organ, relying on the surrounding aqueous humor for nutrient supply and waste removal, making its cells particularly vulnerable to metabolic disturbances and oxidative stress. Any disruption to this delicate homeostatic balance or the structural integrity of its components can lead to the loss of transparency, initiating the process of cataract formation[3].
Molecular and Cellular Mechanisms of Opacification
Section titled “Molecular and Cellular Mechanisms of Opacification”Cataractogenesis fundamentally involves the misfolding and aggregation of lens proteins, primarily crystallins, which consequently impairs light transmission to the retina [9]. Genetic mutations, such as those affecting γC-crystallin, can directly disrupt the intricate hydrogen bond networks within these structural proteins, promoting their aggregation and leading to lens opacity [9]. Beyond direct genetic defects, cellular functions within the lens epithelial cells are also critical, where processes like proliferation and apoptosis can be modulated by epigenetic mechanisms, such as N6-methyladenosine (m6A) modification by METTL3, contributing to conditions like diabetic cataract[18]. Furthermore, oxidative stress, often linked to impaired metabolic processes and the accumulation of reactive oxygen species, plays a significant role in damaging lens proteins and DNA, with genetic polymorphisms in DNA repair enzymes like 8-oxoguanine DNA glycosylase (OGG1) being associated with age-related cataract susceptibility[19]. The lens also exhibits cellular responses to environmental stressors, such as UVB irradiation, which can influence iron metabolism and the expression of ferritin subunits in lens epithelial cells, further impacting oxidative balance[11].
Genetic Basis and Regulatory Networks
Section titled “Genetic Basis and Regulatory Networks”Genetic factors play a substantial role in cataract susceptibility, with twin and family aggregation studies estimating heritability between 35% and 58%[1]. While an extensive body of literature addresses the genetics of childhood cataract, many of these genes are also considered plausible candidates for age-related cataract[2]. Genome-wide association studies (GWAS) have identified numerous genetic loci associated with cataract, including specific genes involved in various cellular functions and regulatory networks[1]. For instance, the ETS transcription factor ERG, located on chromosome 21, has been linked to cataracts in younger individuals, highlighting the role of regulatory elements in lens development and maintenance [3]. Moreover, studies in mouse models have demonstrated that perturbations in genes like Maf, Notch2, E2f, and Brg1, which are crucial for lens biology, can lead to cataract formation, with many candidate genes showing significant differences in gene expression in such models[1]. The FTO gene, primarily known for its association with obesity, has also been linked to nuclear cataract in certain populations, suggesting complex genetic interplay with systemic conditions[2].
Systemic and Environmental Risk Factors
Section titled “Systemic and Environmental Risk Factors”In addition to genetic predispositions, a multitude of systemic and environmental factors contribute to cataract development. Age is the most prominent risk factor, with the prevalence of cataracts increasing significantly in older populations[2]. Lifestyle and health conditions also play a critical role; for example, a higher body mass index (BMI) is associated with an increased risk of cortical and posterior subcapsular cataracts[2]. Environmental exposures such as chronic sunlight (UVB) exposure are known risk factors for lens opacities [10]. Smoking is another significant modifiable risk factor, with studies showing that smoking cessation can reduce the risk of cataract extraction[13]. Furthermore, certain medications, particularly corticosteroids, have been demonstrated to influence cataract formation[16]. Women generally exhibit a slightly higher risk of developing cataracts than men, indicating potential sex-specific effects in disease susceptibility[1]. These various factors often interact with an individual’s genetic makeup, influencing the overall pathophysiological processes that lead to lens opacification [20].
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Genetic Determinants and Lens Gene Expression Control
Section titled “Genetic Determinants and Lens Gene Expression Control”Cataract development is significantly influenced by genetic factors, with numerous susceptibility loci identified through extensive research. Common genetic variants in genes such as SOX-2 are known to contribute to age-related nuclear cataract, highlighting the role of specific genetic predispositions[4]. Large-scale multiethnic genome-wide association studies (GWAS) have further revealed a complex genetic architecture underlying cataract, pinpointing new risk loci and demonstrating sex-specific effects, which collectively underscore the critical impact of inherited factors on lens health[1]. These genetic insights indicate that the precise regulation of gene expression within lens cells is paramount for maintaining transparency and preventing opacification.
The integrity of the lens relies on the tightly controlled expression of genes orchestrated by key regulatory molecules. Transcription factors, including SOX-2, MAFG, and MAFK, are essential for directing the gene expression programs necessary for proper lens development and function; their dysregulation is directly implicated in cataract formation[4]. Similarly, the E2F family of transcription factors (E2F1, E2F2, E2F3) plays a crucial role, as evidenced by cataract development in mice with combined lens-specific knockouts of these genes[1]. Beyond transcription factors, chromatin remodeling, such as that mediated by BRG1, also influences gene accessibility and expression, with dominant negative expression of BRG1 in the lens leading to cataract, emphasizing the importance of epigenetic regulation in lens integrity[1].
Cellular Communication and Developmental Pathways
Section titled “Cellular Communication and Developmental Pathways”Maintaining the unique structure and transparency of the ocular lens is dependent on intricate cellular communication and precisely regulated developmental signaling pathways. The NOTCH signaling pathway exemplifies such a critical system, where its proper function is indispensable for lens development and ongoing homeostasis [1]. Specific disruption, such as lens-specific conditional knockout of Notch2 in mice, directly results in cataract formation, demonstrating the pathway’s fundamental involvement in preventing lens opacification[1].
This pathway’s complex receptor activation and subsequent intracellular signaling cascades are crucial for governing key cellular processes within the lens, including cell fate determination, proliferation, and differentiation. Any perturbation or dysregulation of these essential signaling events can disrupt the delicate balance required for lens structural integrity and functional clarity. Such disruptions contribute to the pathology of cataract, affecting both congenital and age-related forms of the condition.
Metabolic Homeostasis and Oxidative Stress Responses
Section titled “Metabolic Homeostasis and Oxidative Stress Responses”Metabolic pathways are central to lens health, providing the necessary energy and maintaining the precise osmotic balance required for transparency. Disruptions in these pathways represent a significant mechanism in the etiology of cataract. Systemic conditions like type 2 diabetes are strongly associated with cataract, indicating that chronic metabolic dysregulation, such as persistent hyperglycemia, can directly trigger lens opacification[2]. This association suggests that altered energy metabolism and potentially increased oxidative stress within lens cells contribute to the development of cataracts.
Moreover, specific inherited metabolic disorders, such as fructose intolerance, have been directly linked to congenital cataract, illustrating how imbalances in fundamental carbohydrate catabolism can compromise lens transparency[2]. The lens, being an avascular tissue, relies primarily on anaerobic glycolysis for its energy requirements; therefore, any impairment to metabolic regulation or flux control can lead to the accumulation of osmotically active substances or reactive oxygen species, ultimately causing protein aggregation and the characteristic clouding of the lens.
Integrated Network Dysregulation in Cataract Etiology
Section titled “Integrated Network Dysregulation in Cataract Etiology”Cataract development is rarely due to a single isolated pathway failure but rather emerges from the complex, integrated dysregulation of multiple interacting biological networks. Pathway crosstalk is evident in the association between specific single-nucleotide polymorphisms (SNPs) on chromosome 3p14.1-3p14.2 and the susceptibility to type 2 diabetes with cataract, demonstrating how genetic factors can influence systemic metabolic health and subsequently impact lens integrity[2]. This interaction highlights a hierarchical regulation where broader systemic metabolic states, often influenced by an individual’s genetic makeup, can cascade into localized lens pathology.
The multifactorial nature of cataract is underscored by the intricate interplay between genetic predispositions, environmental exposures, and systemic health conditions. Large-scale genetic analyses further reveal genetic correlations of cataract with a spectrum of other diseases and traits, suggesting shared underlying biological networks and emergent properties that contribute to disease susceptibility[1]. A comprehensive understanding of these network interactions and the identification of critical points of pathway dysregulation provides essential insights for developing effective primary prevention strategies and potential therapeutic targets for cataract.
Population Studies
Section titled “Population Studies”Cataract, characterized by the opacification of the crystalline lens, is a significant global health concern, standing as the leading cause of blindness worldwide and the primary cause of vision loss in the United States. Its widespread impact also results in substantial healthcare expenditures, accounting for approximately 60% of Medicare costs related to vision[2]. Population studies are crucial for understanding the prevalence, risk factors, and genetic underpinnings of cataract, informing public health strategies and potential primary prevention efforts.
Global Burden and Demographic Patterns
Section titled “Global Burden and Demographic Patterns”Epidemiological studies reveal significant prevalence patterns and demographic associations for cataract across populations. In the United States, summary estimates indicate that 17.2% of adults aged 40 years and older have cataract in at least one eye, with an additional 5.1% having undergone previous cataract surgery[21]. The incidence of cataract is strongly age-related, commonly presenting as a disease of aging, with development typically beginning in individuals aged 40 years and older[1]. Furthermore, women exhibit a slightly higher risk of developing cataract than men[21], [1]. Beyond vision impairment, cataract has been consistently linked to other adverse health outcomes, including an increased risk of falls and higher mortality rates, possibly due to associated systemic conditions[2], [22]. With increasing global life expectancy, the overall number of cataract cases and subsequent surgeries is projected to rise dramatically, underscoring the urgent need for effective primary prevention strategies[2].
Genetic Epidemiology Across Diverse Populations
Section titled “Genetic Epidemiology Across Diverse Populations”Large-scale genomic investigations, leveraging major population cohorts and biobank studies, have significantly advanced the understanding of cataract susceptibility, identifying new genetic risk loci and demonstrating population-specific effects. A comprehensive multiethnic genome-wide association study (GWAS) meta-analysis, combining data from cohorts such as the Genetic Epidemiology Research on Adult Health and Aging (GERA) and the UK Biobank (UKB), and replicated in the 23andMe research cohort, identified novel risk loci and sex-specific genetic effects for cataract[1]. This extensive study included diverse ethnic groups, such as Latino, East Asian, South Asian, and African American populations, highlighting the importance of cross-population comparisons in unraveling the genetic architecture of the disease[1]. Similarly, the Electronic Medical Records and Genomics (eMERGE) network, predominantly focusing on individuals of European descent, conducted GWAS to explore cataract and age-at-diagnosis, identifying several potential susceptibility loci using genotypic data from the Illumina 660W-Quad or 1M-Duo Beadchips[2]. Further research, such as a meta-analysis of GWAS in multiethnic Asian populations, has also pinpointed specific loci associated with age-related nuclear cataract, demonstrating the value of population-specific genetic studies[8]. These large-scale efforts, including polygenic risk score development in East Asian populations, underscore the complex interplay of genetic factors in cataract susceptibility and aim to improve predictive models[3].
Methodological Approaches and Considerations in Population Studies
Section titled “Methodological Approaches and Considerations in Population Studies”Population studies on cataract employ various methodologies, each with specific strengths and limitations that impact the representativeness and generalizability of findings. Many studies utilize case-control designs, often drawing participants from large healthcare systems or biobanks. For example, the eMERGE network identified cataract cases as individuals who underwent cataract extraction or had multiple diagnostic codes, with controls being age-matched individuals without cataract diagnoses based on electronic health records and natural language processing[2]. While this approach provides rich clinical data, the definition of cataract phenotypes can vary; for instance, the multiethnic GWAS meta-analysis by Choquet et al. noted that cataract phenotypes were assessed differently across cohorts, with some relying on electronic health records and ICD codes (e.g., GERA) and others on self-reported data (e.g., UKB and 23andMe)[1]. This heterogeneity in phenotype ascertainment can introduce potential misclassification, although the consistency of SNP effect estimates and successful replication across cohorts often mitigates these concerns [1]. Sample sizes in these studies range from thousands in individual cohorts, such as the eMERGE network’s several thousand participants, to tens of thousands in meta-analyses, like the 20,335 individuals in the discovery set and 7993 in the validation set for an East Asian polygenic risk score study [3]. Such large-scale studies are critical for detecting subtle genetic associations and for adjusting for confounding demographic and clinical factors, including age, sex, diabetes, and body mass index[3].
Frequently Asked Questions About Cataract
Section titled “Frequently Asked Questions About Cataract”These questions address the most important and specific aspects of cataract based on current genetic research.
1. My parents both had cataracts. Will I get them for sure?
Section titled “1. My parents both had cataracts. Will I get them for sure?”Not necessarily for sure, but your risk is higher. Genetic factors play a significant role in cataract susceptibility, with heritability estimated between 35% and 58%. While your family history increases your chances, it doesn’t guarantee you’ll develop them, as other factors are also involved.
2. Why did my sibling get cataracts but I didn’t?
Section titled “2. Why did my sibling get cataracts but I didn’t?”Even within the same family, genetic predispositions can differ. While genetics are a major factor, with heritability up to 58%, you and your sibling inherited different combinations of risk-influencing genetic variants. Environmental exposures and lifestyle choices also contribute to these individual differences, explaining why one sibling might develop them and another might not.
3. Are women more likely to get cataracts than men?
Section titled “3. Are women more likely to get cataracts than men?”Yes, research indicates women tend to have a slightly higher risk of developing cataracts and undergoing cataract surgery compared to men. Large-scale genetic studies have even identified sex-specific genetic effects that contribute to this difference.
4. Can a DNA test predict my cataract risk?
Section titled “4. Can a DNA test predict my cataract risk?”Yes, tools like Polygenic Risk Scores (PRS) show promise in predicting cataract risk. These scores analyze multiple genetic variations across your genome to estimate your individual susceptibility. While still developing, they can offer insights, particularly in diverse populations.
5. Does my ethnic background affect my chances of getting cataracts?
Section titled “5. Does my ethnic background affect my chances of getting cataracts?”Yes, your ethnic background can influence your cataract risk. While much historical research focused on European populations, multiethnic studies are revealing population-specific genetic variants and differing risk factors. This means findings from one group may not fully apply to others, highlighting the importance of diverse research.
6. What can I do to prevent cataracts if they run in my family?
Section titled “6. What can I do to prevent cataracts if they run in my family?”While you can’t change your inherited genetic risk, lifestyle choices are still important for prevention. Limiting environmental exposures and adopting healthy habits can help mitigate your risk. Research is still exploring the full extent of gene-environment interactions, but primary prevention strategies are crucial.
7. Can my lifestyle really overcome my family’s eye history?
Section titled “7. Can my lifestyle really overcome my family’s eye history?”Your lifestyle can significantly influence your risk, even with a family history. While genetic factors account for 35-58% of susceptibility, environmental factors and complex gene-environment interactions also play a role. Adopting preventative strategies can help reduce your overall risk, even if you have a genetic predisposition.
8. I’m younger, but my vision is blurry. Could it be cataracts?
Section titled “8. I’m younger, but my vision is blurry. Could it be cataracts?”While cataracts are most common with age, they can manifest as a developmental disorder in younger individuals, known as congenital or pediatric cataracts. If you’re experiencing blurry vision at a younger age, it’s important to consult an eye care professional for a proper diagnosis.
9. Is it true that cataracts can increase my risk of falling?
Section titled “9. Is it true that cataracts can increase my risk of falling?”Yes, that is true. Beyond just vision impairment, cataracts have been associated with an increased risk of falls. This is likely due to reduced vision affecting depth perception and obstacle avoidance, making daily activities more hazardous.
10. Why do some people never get cataracts even when they’re old?
Section titled “10. Why do some people never get cataracts even when they’re old?”The absence of cataracts in some older individuals is likely due to a combination of favorable genetic factors and protective environmental influences. While many genetic loci are linked to cataract risk, some individuals may have genetic profiles that confer resilience, along with a lifetime of beneficial lifestyle choices.
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] Choquet H, et al. “A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects.”Nat Commun, vol. 12, 2021, p. 3595.
[2] Ritchie MD, et al. “Electronic medical records and genomics (eMERGE) network exploration in cataract: several new potential susceptibility loci.”Mol Vis, vol. 20, 2014, pp. 1281-1295.
[3] Hsu CC, et al. “Polygenic Risk Score Improves Cataract Prediction in East Asian Population.”Biomedicines, vol. 10, no. 9, 2022, p. 2056.
[4] Yonova-Doing, E. “Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.”Commun Biol, vol. 3, no. 1, 11 Dec. 2020, p. 764. PMID: 33311586.
[5] Hammond, C.J. et al. “The heritability of age-related cortical cataract: The twin eye study.”Investig. Ophthalmol. Vis. Sci., 2001, 42:601–605.
[6] Moore, A.T. “Understanding the molecular genetics of congenital cataract may have wider implications for age related cataract.”Investig. Ophthalmol. Vis. Sci., 2004, 45:2505-2510.
[7] Heiba, I.M. et al. “Evidence for a major gene for cortical cataract.”Investig. Ophthalmol. Vis. Sci., 1995, 36:1284-1290.
[8] Liao J, et al. “Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.”Hum Mol Genet, vol. 23, no. 22, 2014, pp. 6119-6128.
[9] Fu, C. et al. “Cataract-causing mutations L45P and Y46D promote γC-crystallin aggregation by disturbing hydrogen bonds network in the second Greek key motif.”Int. J. Biol. Macromol., 2021, 167:470–478.
[10] West, S.K. et al. “Sunlight exposure and risk of lens opacities in a population-based study: The Salisbury Eye Evaluation project.” JAMA, 1998, 280:714–718.
[11] Goralska, M. et al. “Overexpression of H-and L-ferritin subunits in lens epithelial cells: Fe metabolism and cellular response to UVB irradiation.”Investig. Ophthalmol. Vis. Sci., 2001, 42:1721–1727.
[12] Klein, A.P. et al. “Polygenic effects and cigarette smoking account for a portion of the familial aggregation of.” Investig. Ophthalmol. Vis. Sci., 2005, 46:4425-4430.
[13] Lindblad, B.E. et al. “Smoking cessation and the risk of cataract: A prospective cohort study of cataract extraction among men.”JAMA Ophthalmol., 2014, 132:253–257.
[14] Lim, L.S. et al. “Relation of age-related cataract with obesity and obesity genes in an Asian population.”Am J Epidemiol, 2009, 170:463-470.
[15] Lin, H-J. et al. “Single-nucleotide polymorphisms in chromosome 3p14.1- 3p14.2 are associated with susceptibility of type 2 diabetes with cataract.”Mol Vis, 2010, 16:1206-14.
[16] Skalka, H.W. et al. “Effect of corticosteroids on cataract formation.”Arch Ophthalmol, 1980, 98:1773–1777.
[17] Sitadevi, C. et al. “Fructose intolerance associated with congenital cataract. Report of a case.”Indian J Ophthalmol, 1991, 39:133-134.
[18] Yang, J. et al. “N6-methyladenosine METTL3 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract.”Mol. Ther. Nucleic Acids, 2020, 20:111–116.
[19] Liu, X-C. et al. “Association between the 8-oxoguanine DNA glycosylase gene Ser326Cys polymorphism and age-related cataract: A systematic review and meta-analysis.”Int Ophthalmol, 2018, 38:1451–1457.
[20] Hodge, W. G., et al. “Risk factors for age-related cataracts.” Epidemiologic Reviews, vol. 17, 1995, pp. 336–346.
[21] Congdon N, et al. “Prevalence of cataract and pseudophakia/aphakia among adults in the United States.”Archives of Ophthalmology, vol. 122, no. 3, 2004, pp. 420-426.
[22] Clemons TE, et al. “Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13.”Arch Ophthalmol, vol. 122, no. 5, 2004, pp. 716-24.