Peripheral Vascular Disease
Peripheral vascular disease (PVD), often referred to as peripheral artery disease (PAD), is a common circulatory condition characterized by the narrowing of arteries that supply blood to the limbs, most commonly the legs. This reduction in blood flow is primarily caused by atherosclerosis, a process where fatty deposits, or plaque, build up in the artery walls. While various environmental and lifestyle factors contribute to PVD development, an individual’s genetic predisposition plays a significant role in susceptibility to such complex cardiovascular conditions[1]. The advent of genome-wide association studies (GWAS) has enabled researchers to identify specific genetic variants and loci associated with an increased risk for various common diseases, including those affecting the cardiovascular system[2], [3], [1], [4]. These genetic insights contribute to a deeper understanding of the biological mechanisms underlying arterial health and disease progression.
Clinically, PVD can present with a range of symptoms, from intermittent leg pain during exercise (claudication) to severe pain at rest, non-healing wounds, or tissue death (gangrene) in advanced stages. Early detection and effective management are vital to prevent serious complications, which include critical limb ischemia and an elevated risk of systemic cardiovascular events like heart attack and stroke. Management typically involves lifestyle modifications, pharmacological treatments to improve blood flow and control risk factors, and in some cases, revascularization procedures.
PVD poses a substantial public health burden due to its high prevalence, significant impact on patient quality of life, and considerable healthcare expenditures. Ongoing research, including the identification of new genetic susceptibility loci for coronary artery disease[4], offers promising avenues for improved risk prediction, the development of more personalized prevention strategies, and the discovery of novel therapeutic targets to combat this widespread condition.
Limitations of Genetic Studies in Peripheral Vascular Disease
Section titled “Limitations of Genetic Studies in Peripheral Vascular Disease”Genetic research into complex conditions like peripheral vascular disease, particularly through genome-wide association studies (GWAS), faces several inherent limitations that warrant careful consideration when interpreting findings. These challenges stem from study design, the nature of disease phenotypes, and the intricate interplay of genetic and environmental factors.
Methodological and Statistical Challenges
Section titled “Methodological and Statistical Challenges”Initial genetic association studies often operate with modest sample sizes, which can lead to limited statistical power to detect genetic variants with moderate effect sizes. For instance, some initial GWAS have been calculated to have only approximately 50% power to detect an odds ratio of 2.0 [5]. This constraint necessitates a staged study design, incorporating replication and fine-mapping phases to reduce the risk of spurious associations and confirm initial findings [5]. The critical need for replication is underscored by observations where some reported genetic risk factors for acute coronary syndrome failed validation in large-scale replication studies, highlighting the importance of robust confirmation for reliable identification of genetic loci [6].
Furthermore, the integrity of genetic association data hinges on meticulous quality control processes. In large datasets, even minor systematic differences can obscure true genetic signals, making careful quality assurance paramount [2]. While advanced genotype-calling algorithms and filtering heuristics are employed to select single nucleotide polymorphisms (SNPs) for analysis, infallible detection of incorrect genotype calls is not yet possible[2]. Consequently, the criteria for SNP exclusion must balance stringency, to avoid discarding true signals, with leniency, to prevent true signals from being overwhelmed by spurious findings, complicating the interpretation of significance levels in genome-wide studies [2].
Phenotypic Heterogeneity and Generalizability
Section titled “Phenotypic Heterogeneity and Generalizability”The clinical definition of complex diseases like peripheral vascular disease can introduce significant phenotypic heterogeneity within study cohorts, potentially impacting the precision and consistency of genetic association findings. Variations in diagnostic criteria, disease sub-types, or co-morbidities among individuals can dilute genetic signals or lead to inconsistent associations across different studies. This variability in phenotype definition underscores the challenge in accurately capturing the underlying biological mechanisms through broad clinical characterization[5].
Another critical limitation is the potential for population structure to confound genetic inferences in case-control association studies. Ancestral differences between cases and controls can inadvertently create spurious associations or mask true genetic signals [2]. While methods such as EIGENSTRAT correction are applied to mitigate the effects of population stratification [7], the generalizability of identified genetic risk factors across diverse global populations remains a significant concern, particularly if studies are predominantly conducted in specific ancestral groups. This necessitates further research in varied populations to ensure the universal applicability of findings.
Incomplete Genetic Architecture and Environmental Factors
Section titled “Incomplete Genetic Architecture and Environmental Factors”Despite the identification of numerous susceptibility loci for complex diseases, a substantial portion of the genetic heritability often remains unexplained, a phenomenon referred to as “missing heritability.” This suggests that many genetic effects, including those with smaller individual contributions, rare variants, or structural variants, may still be undiscovered due to limitations in current genomic coverage or statistical power [2]. Consequently, current genetic findings may not yet provide a comprehensive genetic profile for clinically useful prediction of disease risk[2], indicating that the failure to detect a prominent association signal does not conclusively exclude the involvement of any given gene [2].
Furthermore, genetic studies often struggle to fully account for the complex interplay between genetic predispositions and environmental factors. The influence of lifestyle, diet, co-morbidities, and other external exposures on the development and progression of peripheral vascular disease, potentially through intricate gene-environment interactions, represents a significant gap in current knowledge. Unmeasured or unaccounted environmental confounders can obscure or modify genetic effects, highlighting the necessity for integrating detailed environmental data into future research to achieve a more comprehensive understanding of disease etiology and to inform more effective prevention and treatment strategies.
Variants
Section titled “Variants”Genetic variations play a crucial role in an individual’s susceptibility to peripheral vascular disease (PVD) and related atherosclerotic conditions. These variants can influence gene expression, protein function, and biological pathways that contribute to vascular health, lipid metabolism, inflammation, and blood clotting. Studies frequently investigate such genetic markers in relation to subclinical atherosclerosis, which includes measures like ankle-brachial index (ABI), coronary artery calcification (CAC), and carotid intima-media thickness (IMT) endothelin Receptor Type A, is part of the endothelin system, which plays a critical role in regulating vascular tone and blood pressure. While variants likers72957606 and rs10305838 in the PRMT5P1 - EDNRA region might theoretically influence vascular constriction and remodeling, specific studies have also indicated that the related EDN1gene did not show significant associations with subclinical atherosclerosis in certain large-scale genetic analyses endothelial health. The presentation patterns are diverse, influenced by genetic predispositions that contribute to inter-individual variation in disease susceptibility and progression[8]. While the research primarily focuses on genetic associations rather than explicit clinical symptom descriptions, these studies highlight the importance of objective measures in identifying early disease phenotypes and assessing severity ranges.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs10455872 rs55730499 | LPA | myocardial infarction lipoprotein-associated phospholipase A(2) measurement response to statin lipoprotein A measurement parental longevity |
| rs4977574 rs1537372 rs1537371 | CDKN2B-AS1 | myocardial infarction coronary artery disease asthma, cardiovascular disease brain aneurysm low density lipoprotein cholesterol measurement |
| rs4766578 rs10774625 | ATXN2 | reticulocyte count Vitiligo smoking initiation coronary artery disease gout |
| rs1894692 | SLC19A2 - F5 | pneumonia blood protein amount atrial fibrillation tissue factor pathway inhibitor amount endometriosis |
| rs181579827 | LINC02233 - LINC02477 | peripheral vascular disease |
| rs573273929 | LRP1B | peripheral vascular disease |
| rs148116280 | IRX1 - LINC02063 | peripheral vascular disease |
| rs149511772 | PRKG1 | peripheral vascular disease |
| rs72957606 rs10305838 | PRMT5P1 - EDNRA | myocardial infarction peripheral vascular disease atherosclerosis heart disease |
| rs597808 | ATXN2 | gastroesophageal reflux disease systolic blood pressure, alcohol drinking diastolic blood pressure, alcohol drinking colorectal cancer, colorectal adenoma systemic lupus erythematosus |
Subclinical Arterial Changes and Risk Stratification
Section titled “Subclinical Arterial Changes and Risk Stratification”Peripheral vascular disease, particularly in its incipient stages, frequently presents as “subclinical atherosclerosis in major arterial territories,” meaning that detectable changes in arterial health occur prior to the manifestation of overt clinical signs or patient-reported symptoms[8]. These early, silent presentations are typically identified through objective “multivariable-adjusted subclinical atherosclerosis measures” rather than subjective patient complaints[8]. Such measurements serve as crucial diagnostic tools, providing significant prognostic indicators for broader cardiovascular disease outcomes and enabling effective risk stratification for future events[8]. The diagnostic value of identifying subclinical atherosclerosis lies in its ability to pinpoint individuals at elevated risk, allowing for potential early interventions to mitigate disease progression.
Genetic Predisposition and Phenotypic Heterogeneity
Section titled “Genetic Predisposition and Phenotypic Heterogeneity”The clinical presentation of peripheral vascular disease exhibits considerable inter-individual variation and phenotypic diversity, particularly as revealed by genetic predispositions identified through genome-wide association studies[8]. These studies pinpoint “susceptibility loci” and “genetic correlates” for cardiovascular disease outcomes, suggesting that specific genetic factors contribute to the varying patterns and severity ranges of arterial involvement[3]. Measurement approaches involve sophisticated statistical analyses, such as Cox proportional hazards and logistic regression, to assess associations between specific genetic variants and disease phenotypes, serving as objective measures of genetic risk[8].
The identification of these genetic markers holds significant diagnostic value by offering insights into an individual’s predisposition to developing peripheral vascular disease, even in the absence of traditional clinical signs[2]. This genetic information can help differentiate between various phenotypic expressions of arterial disease and may serve as an early prognostic indicator, guiding personalized prevention strategies and informing the understanding of age-related changes and other demographic variability in disease risk[3]. Understanding this heterogeneity is crucial for refining prognostic models and guiding clinical management.
Causes
Section titled “Causes”Peripheral vascular disease (PVD) is a complex condition influenced by a combination of genetic predispositions and various external factors that contribute to its development and progression. Research into related cardiovascular diseases, such as coronary artery disease, provides insight into the underlying causal mechanisms.
Genetic Architecture and Polygenic Risk
Section titled “Genetic Architecture and Polygenic Risk”Peripheral vascular disease, similar to other common cardiovascular conditions, is significantly influenced by an individual’s genetic makeup. Genome-wide association studies (GWAS) have been instrumental in identifying numerous inherited variants, particularly single nucleotide polymorphisms (SNPs), that contribute to disease susceptibility[1]. These studies reveal a polygenic risk model, where the cumulative effect of multiple genetic loci, each conferring a small increase in risk, collectively determines an individual’s overall predisposition. The Framingham Heart Study, for example, has conducted extensive genome-wide associations for cardiovascular disease outcomes, identifying various candidate genes that play a role in disease etiology[8].
Identified Genetic Loci and Their Implications
Section titled “Identified Genetic Loci and Their Implications”Beyond the general concept of polygenic risk, specific genetic loci have been pinpointed as contributing to conditions like coronary artery disease, which shares pathophysiological underpinnings with PVD. For instance, a new susceptibility locus for coronary artery disease has been identified on chromosome 3q22.3, highlighting a particular genomic region where variations can influence vascular health[8]. The ongoing identification of these loci through large-scale genetic studies, including efforts by consortia like the Wellcome Trust Case Control Consortium, underscores the complex genetic landscape of such diseases. These findings suggest that variations in these specific regions can modulate disease risk and progression through mechanisms yet to be fully elucidated.
Age-Related and External Influences on Risk
Section titled “Age-Related and External Influences on Risk”Beyond direct genetic predisposition, other factors significantly modulate the risk of peripheral vascular disease. Age is a prominent contributing factor, with research from the Framingham Study exploring genetic correlates of “longevity and selected age-related phenotypes”[8], indicating that the risk for PVD can increase over a lifetime, often influenced by an individual’s genetic background. Furthermore, while genetic factors provide substantial insight into susceptibility, studies suggest that genetic variants alone, even in combination, do not yet offer “clinically useful prediction of disease”[2]. This implies that the full manifestation of PVD also involves complex interactions between an individual’s genetic profile and various external influences throughout life, shaping how genetic predispositions are expressed or modified.
Pathophysiological Mechanisms and Systemic Consequences
Section titled “Pathophysiological Mechanisms and Systemic Consequences”Peripheral vascular disease (PVD) is a condition driven by pathophysiological processes that impact major arterial territories throughout the body, excluding those specifically supplying the heart and brain[8]. This disease manifests as a disruption of normal arterial function, often involving subclinical atherosclerosis, which signifies the early stages of arterial hardening and narrowing[8]. Such widespread arterial pathology contributes significantly to various cardiovascular disease outcomes, underscoring the systemic nature and broad tissue-level interactions involved in its progression[3]. The development of PVD thus represents a profound homeostatic disruption within the vascular system, leading to impaired blood flow and potential organ-specific effects.
Genetic Architecture of Vascular Risk
Section titled “Genetic Architecture of Vascular Risk”Genetic mechanisms play a crucial role in predisposing individuals to peripheral vascular disease, with insights largely derived from genome-wide association studies (GWAS) focused on related conditions like coronary artery disease[1]. These studies systematically identify genetic risk variants across the human genome, revealing specific gene functions and regulatory elements that influence disease susceptibility[2]. For instance, a new susceptibility locus for coronary artery disease has been pinpointed on chromosome 3q22.3, illustrating how particular genomic regions are implicated in vascular health and disease progression[4]. Such findings highlight the complex genetic architecture underlying arterial pathologies, where numerous genes and their regulatory networks contribute to an individual’s overall risk profile.
Molecular and Cellular Pathways in Disease Progression
Section titled “Molecular and Cellular Pathways in Disease Progression”While direct detailed pathways for peripheral vascular disease are complex, genetic research into related conditions offers insights into molecular and cellular contributions. Studies on other inflammatory or autoimmune diseases have identified genetic variants linked to critical cellular functions, such as the immune response[9], or metabolic processes like autophagy [10]. These findings suggest that dysregulation of similar molecular pathways and cellular functions, including signaling pathways and regulatory networks, likely underlies the pathogenesis of vascular diseases. The integrity and function of arterial cells are governed by intricate molecular events, and disruptions in these processes contribute to disease development.
Key Biomolecules and Regulatory Influences
Section titled “Key Biomolecules and Regulatory Influences”The progression of peripheral vascular disease is influenced by key biomolecules, including critical proteins, enzymes, receptors, and transcription factors, whose functions are often modulated by genetic variations. Gene expression patterns, regulated by both genetic and potentially epigenetic modifications, dictate the levels and activities of these biomolecules within arterial tissues. For example, specific alleles of theAPOEgene, a critical protein involved in lipid metabolism, have been identified as modifiers of risk for other complex neurological diseases, suggesting broader implications for cardiovascular health due to their fundamental biological roles[11]. These biomolecular players are central to the homeostatic balance of the vasculature, and their dysregulation can lead to the pathological changes observed in PVD.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Inflammation and Immune Signaling in Vascular Disease
Section titled “Inflammation and Immune Signaling in Vascular Disease”Vascular inflammation is a fundamental driver in the development of peripheral vascular disease, initiating with the activation of endothelial cells by various stimuli within the arterial wall. This activation involves specific receptor-ligand interactions that trigger intricate intracellular signaling cascades, such as the NF-κB pathway, which subsequently regulate the transcription of genes encoding adhesion molecules and pro-inflammatory cytokines. These molecular events promote the recruitment and infiltration of immune cells, including monocytes, into the sub-endothelial space, establishing a chronic inflammatory state that is often perpetuated by positive feedback loops[1]. Genetic variants identified through genome-wide association studies can influence the efficiency or intensity of these signaling pathways, thereby modulating an individual’s inflammatory response and overall susceptibility to vascular disease[2].
Lipid Metabolism and Atherogenic Processes
Section titled “Lipid Metabolism and Atherogenic Processes”Dysregulated lipid metabolism is central to the pathophysiology of peripheral vascular disease, primarily through the accumulation of modified lipoproteins within the arterial wall, a hallmark of atherosclerosis. Key metabolic pathways govern the biosynthesis, transport, and catabolism of cholesterol and triglycerides, with their precise flux tightly controlled by a network of enzymes and regulatory proteins. For instance, impaired clearance or excessive production of low-density lipoproteins (LDL) leads to their retention and subsequent oxidation, triggering downstream cellular responses that contribute to plaque formation. Genetic variants can significantly impact these metabolic pathways, altering lipid profiles and thus influencing the overall metabolic regulation and individual risk for developing subclinical atherosclerosis[8], [3].
Vascular Cell Dynamics and Remodeling
Section titled “Vascular Cell Dynamics and Remodeling”The structural integrity and functional adaptability of peripheral arteries are maintained by complex cellular dynamics, encompassing the proliferation and migration of vascular smooth muscle cells (VSMCs) and endothelial cells, alongside continuous extracellular matrix (ECM) remodeling. These processes are meticulously controlled by various growth factor signaling pathways, which activate intracellular cascades that regulate the gene expression for cell cycle progression, cellular migration, and the synthesis or degradation of ECM components. Post-translational modifications, such as phosphorylation or allosteric control of key enzymes, finely tune the activity and stability of regulatory proteins involved in these cellular events, ensuring proper vascular architecture. However, in peripheral vascular disease, dysregulation of these finely balanced pathways leads to maladaptive remodeling, characterized by excessive VSMC proliferation and migration, ultimately contributing to plaque growth and vessel narrowing[1].
Genetic and Transcriptional Regulation of Vascular Health
Section titled “Genetic and Transcriptional Regulation of Vascular Health”Genetic factors play a critical role in predisposing individuals to peripheral vascular disease, profoundly influencing the intricate networks of gene regulation that maintain vascular homeostasis. Specific transcription factors, often activated by upstream signaling events or metabolic cues, bind to regulatory regions of DNA to control the precise expression of genes involved in inflammation, lipid metabolism, and vascular remodeling. These regulatory mechanisms operate under complex hierarchical control and are characterized by extensive pathway crosstalk, where the output of one pathway can modulate the activity of another, leading to integrated physiological responses. Genetic variants identified through genome-wide association studies, such as the susceptibility locus on chromosome 3q22.3, can alter these critical transcriptional programs, leading to emergent properties of disease susceptibility and progression[4], [2].
Clinical Relevance
Section titled “Clinical Relevance”Early Detection and Risk Stratification
Section titled “Early Detection and Risk Stratification”The early identification of peripheral vascular disease (PVD) and individuals at elevated risk is crucial for timely intervention and improved patient outcomes. The Ankle-Brachial Index (ABI) is a fundamental diagnostic tool, and its measurement project has been a focus within large-scale studies such as the Framingham Heart Study[8]. Such initiatives, alongside genome-wide association studies (GWAS), aim to identify genetic associations with subclinical atherosclerosis across various arterial territories, providing insights into an individual’s predisposition to cardiovascular disease outcomes, including PVD[3].
While genetic variants have been uncovered for conditions like coronary artery disease and subclinical atherosclerosis, their standalone utility in providing clinically useful prediction of disease has been noted as limited[2]. Nevertheless, combining genetic insights with established traditional risk factors, such as diabetes, hypertension, and hyperlipidemia, can enhance risk assessment[1]. This integrated approach allows for more precise risk stratification, enabling healthcare providers to identify high-risk individuals and implement personalized prevention strategies before the onset of overt symptoms.
Prognostic Value and Disease Progression
Section titled “Prognostic Value and Disease Progression”Peripheral vascular disease, as a manifestation of systemic atherosclerosis, carries significant prognostic implications for a patient’s overall cardiovascular health[1]. The presence of subclinical atherosclerosis in various major arterial territories serves as a strong predictor of future cardiovascular events and indicates the potential for disease progression[8]. Consequently, monitoring the development and extent of atherosclerosis in peripheral arteries can help clinicians anticipate long-term outcomes and tailor management strategies to mitigate adverse events.
Genetic associations with cardiovascular disease outcomes and subclinical atherosclerosis offer a deeper understanding of the biological pathways that influence how PVD progresses[3]. By integrating these genetic predispositions with clinical markers, clinicians can refine predictions about the disease’s trajectory and make informed decisions regarding the intensity of therapeutic interventions[1]. This comprehensive approach supports the development of personalized management plans aimed at improving long-term health and preventing severe complications.
Systemic Atherosclerosis and Comorbidities
Section titled “Systemic Atherosclerosis and Comorbidities”Peripheral vascular disease is intimately connected to systemic atherosclerosis, sharing common pathophysiological mechanisms and risk factors with coronary artery disease (CAD)[1]. Patients diagnosed with PVD frequently present with coexisting CAD or cerebrovascular disease, illustrating the widespread nature of the atherosclerotic process throughout the body[1]. This systemic perspective emphasizes the need for a holistic approach to patient care, as addressing PVD inherently contributes to reducing the risk of other major cardiovascular complications.
The prevalence of traditional cardiovascular risk factors, including diabetes, hypertension, and hyperlipidemia, significantly increases the likelihood of developing both PVD and CAD[1]. Therefore, effective management of these comorbidities is paramount for preventing the initiation and advancement of PVD and its associated complications, such as critical limb ischemia and amputation [1]. A thorough understanding of these interconnected conditions guides clinicians in providing comprehensive care that targets the full spectrum of atherosclerotic disease in their patients.
Frequently Asked Questions About Peripheral Vascular Disease
Section titled “Frequently Asked Questions About Peripheral Vascular Disease”These questions address the most important and specific aspects of peripheral vascular disease based on current genetic research.
1. My parent has PVD; will I get it too?
Section titled “1. My parent has PVD; will I get it too?”While your genetic predisposition plays a significant role in your susceptibility to PVD, it’s not a guarantee. You inherit a tendency, but environmental and lifestyle factors also heavily influence whether you develop the condition. Focusing on a healthy lifestyle can help mitigate your inherited risk.
2. Why do some healthy people still get PVD?
Section titled “2. Why do some healthy people still get PVD?”Even with a healthy lifestyle, an individual’s genetic makeup can increase their risk for PVD. Researchers have identified specific genetic variants that contribute to susceptibility, meaning some people are predisposed regardless of other factors. It highlights the complex interplay between genes and environment.
3. Can my diet and exercise really beat my PVD genes?
Section titled “3. Can my diet and exercise really beat my PVD genes?”Yes, your lifestyle choices, including diet and exercise, play a crucial role. While genetics contribute to your risk, there’s a complex interaction with environmental factors. Lifestyle modifications are a cornerstone of PVD management and can significantly reduce your risk and improve outcomes, even with a genetic predisposition.
4. Should I get a DNA test to check my PVD risk?
Section titled “4. Should I get a DNA test to check my PVD risk?”Current genetic findings, primarily from genome-wide association studies (GWAS), have identified many susceptibility loci for PVD. However, these findings don’t yet provide a comprehensive genetic profile for clinically useful prediction of individual disease risk. Genetic tests might offer insights, but they aren’t definitive for personal risk prediction yet.
5. Does my ancestry change my PVD risk profile?
Section titled “5. Does my ancestry change my PVD risk profile?”Yes, it can. The generalizability of identified genetic risk factors across diverse global populations is a significant concern, as many studies are predominantly conducted in specific ancestral groups. This means your ethnic background might influence your specific genetic risk factors, and more research is needed in varied populations.
6. Why are my PVD symptoms different from others?
Section titled “6. Why are my PVD symptoms different from others?”The clinical presentation of PVD can vary significantly between individuals. This “phenotypic heterogeneity” means that differences in diagnostic criteria, specific disease subtypes, or other co-existing health conditions can lead to diverse symptoms. Your unique genetic makeup also influences how the disease manifests.
7. Why might PVD treatments work better for some?
Section titled “7. Why might PVD treatments work better for some?”The variability in how PVD presents and progresses, partly due to genetic differences, can influence treatment effectiveness. Ongoing research aims to identify new genetic susceptibility loci to develop more personalized prevention strategies and novel therapeutic targets, tailoring treatments to individual genetic profiles.
8. I’m active, but still have leg pain. Why me?
Section titled “8. I’m active, but still have leg pain. Why me?”Even if you maintain an active lifestyle, your genetic predisposition can make you more susceptible to developing PVD and experiencing symptoms like claudication. Genetics play a significant role in determining who is at higher risk for conditions like PVD, even in the absence of traditional lifestyle risk factors.
9. Can I protect my kids from my PVD risk?
Section titled “9. Can I protect my kids from my PVD risk?”You can empower your children by encouraging a healthy lifestyle from a young age, including a balanced diet and regular exercise. While they may inherit some genetic predisposition from you, these lifestyle modifications are vital for preventing or delaying the onset of PVD and its complications.
10. Why does my PVD seem to progress so quickly?
Section titled “10. Why does my PVD seem to progress so quickly?”The rate of PVD progression can vary significantly among individuals, influenced by both genetic factors and environmental exposures. Genetic insights contribute to understanding the biological mechanisms underlying disease progression, suggesting that certain genetic profiles may lead to a more rapid advancement of the condition.
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] Samani NJ, et al. “Genomewide association analysis of coronary artery disease.”N Engl J Med, vol. 357, no. 5, 2007, pp. 443-53.
[2] Wellcome Trust Case Control Consortium. “Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.” Nature, 2007.
[3] Larson MG, et al. “Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes.”BMC Med Genet, vol. 8, suppl. 1, 2007, p. S5.
[4] Erdmann J, et al. “New susceptibility locus for coronary artery disease on chromosome 3q22.3.”Nat Genet, vol. 41, no. 9, 2009, pp. 996-1000.
[5] Burgner, D. et al. “A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease.”PLoS Genet, vol. 5, no. 1, 2009, p. e1000319.
[6] Morgan, T. M. et al. “Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study.” JAMA, vol. 297, no. 14, 2007, pp. 1551-61.
[7] Garcia-Barcelo, M. M. et al. “Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung’s disease.”Proc Natl Acad Sci U S A, vol. 106, no. 8, 2009, pp. 2694-99.
[8] O’Donnell, C. J. “Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study.”BMC Med Genet, 2007.
[9] Hunt, K. A., et al. “Newly identified genetic risk variants for celiac disease related to the immune response.”Nat Genet, 2008.
[10] Rioux, John D., et al. “Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis.”Nat Genet, 2007.
[11] Reiman, Eric M., et al. “GAB2 alleles modify Alzheimer’s risk in APOE epsilon4 carriers.” Neuron, 2007.