Disease Progression
Introduction
Background
Disease progression describes the natural course and evolution of a medical condition over time, encompassing its onset, development through various stages, and eventual outcomes. This fundamental concept in medicine provides a framework for understanding the trajectory of an illness within an individual, including periods of worsening symptoms (exacerbations), improvement (remissions), and stability. A thorough understanding of disease progression is essential for both clinical practice and medical research, impacting how diseases are characterized, managed, and studied across a broad spectrum of human health conditions.
Biological Basis
At its core, disease progression is a complex biological phenomenon influenced by a multifaceted interplay of genetic factors, environmental exposures, and lifestyle choices. Genetic variations, such as single nucleotide polymorphisms (SNPs), can significantly modulate the rate and severity of a disease's advancement. These genetic markers may affect gene expression, alter protein function, or influence critical cellular pathways involved in the disease process, thereby dictating how quickly a condition progresses or how an individual responds to therapeutic interventions. Research into these genetic determinants helps identify individuals who may be at higher risk for aggressive disease courses or those who might derive the most benefit from specific treatments.
Clinical Relevance
Clinically, understanding disease progression is paramount for accurate diagnosis, providing prognostic information, and developing effective, personalized treatment strategies. Healthcare professionals rely on knowledge of typical disease trajectories to counsel patients, manage expectations, and tailor care plans to individual needs. The identification of genetic markers associated with progression enables a precision medicine approach, allowing for early intervention in high-risk individuals or the selection of therapies most likely to slow disease advancement. This is particularly crucial in conditions with variable courses, such as Parkinson's disease or inflammatory bowel diseases like Crohn's disease, where genetic insights can help predict individual patient outcomes and guide therapeutic decisions. [1], [2], [3], [4]
Social Importance
The social importance of understanding disease progression extends broadly to public health, individual quality of life, and economic considerations. For patients, a clear understanding of their disease's likely course empowers them to make informed decisions regarding their care, lifestyle adjustments, and future planning. From a societal perspective, insights into disease progression inform public health initiatives, aid in the equitable allocation of healthcare resources, and guide the development of preventative strategies. Effective management of disease progression can alleviate the burden on healthcare systems, improve patient outcomes, and enhance overall public well-being, contributing to a healthier and more productive society.
Methodological and Statistical Constraints
Even with large cohorts, current genome-wide association studies (GWAS) often have limited statistical power to detect common genetic variants with modest effect sizes (e.g., odds ratio < 1.2) or rarer, more penetrant alleles that may influence disease progression . These phenotypes are crucial as they can serve as early indicators, allowing for the study of disease pathogenesis before the onset of symptomatic illness. [5] For instance, left ventricular (LV) chamber size, wall thickness (LV remodeling), and mass (LVM) are considered intermediate phenotypes in the progression to high blood pressure, stroke, and heart failure. [5]
The study of disease progression also encompasses the continuous worsening of metabolic risk factors across the spectrum of conditions like nondiabetic glucose tolerance, which can longitudinally lead to microalbuminuria and incident cardiovascular events. [6] This perspective highlights a "life course approach" to chronic disease epidemiology, acknowledging that disease development is a continuum rather than a sudden event. [7] Subclinical disease, such as early atherosclerosis or renal changes, is recognized as an independent risk factor for future clinical events, emphasizing the importance of identifying and characterizing these early stages of progression. [8]
Classification Systems and Severity Gradations
Classification systems for disease progression integrate both categorical and dimensional approaches to characterize the evolving nature of illness. Diseases such as cardiovascular disease (CVD), stroke, heart failure, and type II diabetes mellitus are broadly classified based on established diagnostic criteria. [5] Within these classifications, severity gradations are often applied to describe the stage or extent of progression. For example, echocardiographic measurements can be categorized using height- and sex-specific classifications to assess the severity of cardiac remodeling. [5]
The progression of conditions like subclinical atherosclerosis is classified using specific imaging-based measures, including coronary artery calcification (CAC), abdominal aortic calcification (AAC), and carotid intima-media thickness (IMT). [9] These measures, often quantified by scores like the modified Agatston Score for calcification, provide dimensional data that can indicate increasing severity and risk. [9] Similarly, chronic kidney disease (CKD) is defined and classified based on criteria from organizations like the National Kidney Foundation Kidney Disease Outcome Quality Initiative, often incorporating estimated glomerular filtration rate (GFR) and urinary albumin/creatinine ratio (UACR) to stage the disease. [10] The concept of "morbidity-free survival," defined as achieving a certain age free of conditions like CVD, dementia, and cancer, offers a categorical outcome for assessing overall health progression over a lifespan. [11]
Diagnostic Criteria, Measurement Approaches, and Terminology
Precise diagnostic and measurement criteria are fundamental to assessing disease progression, relying on a combination of clinical observations, quantitative biomarkers, and imaging techniques. Clinical criteria for conditions like diabetes are operationally defined by thresholds such as fasting blood sugar ≥126 mg/dL or random blood sugar of ≥200 mg/dL. [11] Research criteria often involve sophisticated measurement approaches, including carotid ultrasonography for IMT, multidetector computed tomography (MDCT) for CAC and AAC, and ankle-brachial systolic blood pressure for the ankle brachial index (ABI). [9] Specific thresholds, such as CT attenuation >130 Hounsfield Units for calcified lesions, are used to objectively define the presence and extent of these subclinical manifestations. [9]
Key terminology encompasses a wide array of biomarkers and physiological assessments. Echocardiography measures traits like LVM, while brachial artery endothelial function is assessed via flow-mediated dilation (FMD), and cardiac stress is evaluated through exercise treadmill stress testing (ETT). [5] Pulmonary function progression is measured by spirometry data, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), with rates of decline calculated from longitudinal data. [12] Beyond imaging and functional tests, numerous plasma and serum biomarkers are measured, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 soluble receptor (IL-6sR), and various metabolic factors like glycemia, insulin resistance, and lipid profiles. [13] Standardized vocabularies and accession numbers, such as those from Swissprot for proteins (e.g., SHBG - PO4278) and Ensembl for genes (e.g., ABO - ENSG00000175164), ensure consistent nomenclature across research efforts. [14]
Genetic Predisposition and Complex Inheritance
Disease progression is significantly shaped by an individual's genetic makeup, encompassing both common inherited variants and rarer Mendelian forms. Genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) contributing to the risk and trajectory of various conditions, such as common genetic variation near MC4R influencing waist circumference and insulin resistance, and specific variants associated with adult and childhood obesity. [15] These genetic contributions often involve polygenic risk, where the cumulative effect of multiple genes, rather than a single gene, determines susceptibility and progression.
Beyond individual variants, gene-gene interactions play a crucial role in modifying disease risk and progression. For instance, GAB2 alleles are known to modify Alzheimer's risk in carriers of the APOE epsilon4 genotype, illustrating how combinations of genetic factors can profoundly alter disease susceptibility. [16] Similarly, specific alpha-Synuclein gene haplotypes have been associated with Parkinson's disease, and mutations in genes like parkin can lead to autosomal recessive juvenile parkinsonism, highlighting both common complex trait inheritance and rarer Mendelian forms that dictate disease onset and severity. [17] The heritability of intermediate phenotypes, such as echocardiographic dimensions, brachial artery endothelial function, and treadmill exercise responses, further underscores the extensive genetic underpinnings of many aspects of disease progression. [5]
Environmental Exposures and Lifestyle Modifiers
Environmental factors and lifestyle choices exert substantial influence on disease progression by interacting with an individual's inherent susceptibilities. Dietary patterns, physical activity levels, and exposure to various substances can accelerate or mitigate disease development. For example, smoking is a recognized lifestyle factor that can impact inflammatory markers like CD40 Ligand, thereby contributing to disease pathways. [13]
Beyond individual behaviors, broader environmental influences such as socioeconomic status and geographic location also play a role. Research indicates that lifecourse influences on health, including the region of residence during childhood and adulthood, can significantly affect health outcomes, suggesting a complex interplay between an individual's environment over time and their disease trajectory. [18] These external factors can modulate physiological processes, influence gene expression, and directly contribute to the manifestation and severity of various health conditions, working in concert with or sometimes overriding genetic predispositions.
Gene-Environment Dynamics and Developmental Influences
Disease progression is frequently a consequence of intricate gene-environment interactions, where an individual's genetic predisposition is activated or exacerbated by specific environmental triggers. The impact of genes and environments in explaining conditions like Alzheimer's disease exemplifies this dynamic, where genetic vulnerabilities may only lead to disease in the presence of certain environmental exposures or lifestyle factors. [19] This interaction highlights that genetic risk is not always deterministic but often probabilistic, depending on the environmental context.
Furthermore, developmental and early life influences can establish foundational pathways for future disease progression. Factors encountered during childhood, such as those contributing to childhood obesity, can have long-lasting effects on metabolic health and disease risk in adulthood. [20] The concept of early life experiences shaping later health outcomes is consistent with developmental programming that influences disease trajectories.
Acquired Conditions and Age-Related Changes
The progression of a disease is often modulated by the presence of other acquired health conditions and the natural process of aging. Comorbidities, or co-occurring diseases, can significantly complicate a patient's health status and accelerate the decline associated with a primary condition. For instance, intermediate phenotypes such as left ventricular hypertrophy, endothelial dysfunction, and abnormal treadmill exercise responses are established risk factors and precursors for overt cardiovascular disease, demonstrating how acquired physiological changes contribute to disease progression. [5]
Age-related changes represent a universal factor influencing disease progression, with many conditions exhibiting increased incidence and severity with advancing age. The effects of age are critical in understanding the association between genetic factors, such as the APOE genotype, and the risk of diseases like Alzheimer's. [21] Moreover, the age at onset for certain neurodegenerative diseases, including Parkinson's disease, is itself genetically controlled, indicating that an individual's genetic blueprint can influence when age-related factors begin to manifest as disease. [22]
Biological Background of Disease Progression
Understanding disease progression requires a comprehensive view of the intricate biological mechanisms that span from genetic predispositions to systemic effects. This involves dissecting how molecular pathways become dysregulated, how genetic and epigenetic factors confer susceptibility, how immune responses shape disease trajectory, and how these changes manifest at the tissue and organ levels. The progression of various diseases, from neurodegenerative disorders to cardiovascular conditions and inflammatory diseases, often shares common underlying biological themes, even if the specific molecules and cells involved differ.
Genetic and Epigenetic Underpinnings of Susceptibility
Genetic factors are fundamental in determining an individual's susceptibility to various diseases and influencing their progression. For example, specific alleles of the GAB2 gene can modify the risk of Alzheimer's disease, especially in individuals carrying the APOE epsilon4 allele. [16] In neurodegenerative contexts, mutations in the parkin gene are known to cause autosomal recessive juvenile parkinsonism, while specific haplotypes of the alpha-Synuclein gene are associated with Parkinson's disease, underscoring the role of inherited genetic variations in disease onset and course. [23] Beyond neurodegeneration, genetic variants also influence inflammatory conditions, with genes like NELL1 identified as novel susceptibility genes for inflammatory bowel disease (IBD), and allelic variants of the ABCB1 (MDR1) gene also linked to IBD. [1]
The interplay of genetic elements extends to complex traits and systemic conditions, where gene polymorphisms can modulate biomarker levels and disease risk. For instance, polymorphisms within the C-reactive protein gene contribute to the variability in serum C-reactive protein levels, an important inflammatory marker. [24] Genetic studies have also revealed common variants associated with widespread conditions such as adult and childhood obesity. [20] Furthermore, research into longevity and healthy aging phenotypes suggests that genes involved in DNA repair and the evolutionarily conserved insulin/insulin-like growth factor signaling pathway may hold promise for understanding human lifespan regulation. [11]
Disruption of Cellular Signaling and Homeostasis
The precise regulation of cellular signaling pathways and the maintenance of homeostasis are critical for normal physiological function, and their disruption is a hallmark of disease progression. In Alzheimer's disease, Presenilins are known to mediate the activation of phosphatidylinositol 3-kinase/AKT and ERK signaling pathways through specific receptors, indicating their role in cellular communication that can be altered in disease. [25] Similarly, the SEMA5A gene, characterized by its sema domain and thrombospondin repeats, has been implicated in the apoptosis pathway, a programmed cell death mechanism often dysregulated in various diseases, including neurodegenerative disorders. [3]
Homeostatic imbalances can also arise from failures in essential cellular processes, such as protein degradation and second messenger signaling. The ubiquitin pathway, crucial for protein turnover, is disrupted in Parkinson's disease, leading to the accumulation of misfolded proteins. [26] In cardiovascular disease, the TGF-beta signaling pathway, mediated by Smad proteins, plays a role in cellular responses, while Angiotensin II is known to increase phosphodiesterase 5A expression in vascular smooth muscle cells, thereby antagonizing cGMP signaling and contributing to vascular dysfunction. [27] Furthermore, the disruption of the CFTR chloride channel can alter the mechanical properties and cAMP-dependent chloride transport in aortic smooth muscle cells, indicating a broader impact on cellular function across different organ systems. [28]
Immune Dysregulation and Inflammatory Processes
Immune dysregulation and chronic inflammation are central to the progression of many diseases, driving tissue damage and influencing systemic health. Key inflammatory biomarkers, such as CD40 Ligand, osteoprotegerin, P-selectin, tumor necrosis factor receptor 2, and tumor necrosis factor-alpha, are indicators of underlying inflammatory and oxidative stress processes. [13] Systemic inflammation, for instance, is a recognized contributor to the progression of chronic obstructive pulmonary disease (COPD). [29] The interleukin-18 system also plays a significant role in cardiovascular disease, with genetic analyses highlighting the involvement of the interleukin-18 gene in this pathology. [30]
In inflammatory bowel diseases, the immune response is particularly critical, involving complex interactions between epithelial defense mechanisms and both innate and adaptive immunity. [4] Proteins like MST1 (macrophage stimulatory protein 1) are directly involved in inflammation and the subsequent tissue remodeling required for wound healing. [4] Additionally, APEH (APH), a serine peptidase, contributes to gut health by degrading bacterial peptide breakdown products, which helps prevent an excessive immune response. [4] These examples illustrate how tightly regulated immune and inflammatory pathways are essential for maintaining tissue integrity and preventing disease exacerbation.
Tissue and Organ-Level Pathology
The cumulative effects of genetic predispositions, cellular signaling disruptions, and immune dysregulation manifest as distinct pathologies at the tissue and organ levels, defining the observable progression of disease. In Alzheimer's disease, the atrophy of the hippocampus, measurable by MRI, is a predictor of disease in individuals with mild cognitive impairment. [31] Furthermore, the activation of specific brain regions vulnerable to Alzheimer's disease is observed even in the early stages of mild cognitive impairment. [32] These changes reflect the neurodegenerative process impacting cognitive function and brain structure.
In cardiovascular diseases, the progression involves the development of lesions within arterial territories. The natural history of aortic and coronary atherosclerotic lesions, which can begin in youth, underscores a long-term pathological process that leads to conditions like coronary artery disease. [33] Such progression can result in significant systemic consequences, including altered pulmonary function, as evidenced by quantitative spirometric phenotypes used to assess lung health. [12] Moreover, tissue-specific proteins, such as BSN (a scaffolding protein expressed in axons), contribute to the structural integrity and function of specific tissues, and their disruption can contribute to organ-specific pathologies. [4]
Pathways and Mechanisms
Disease progression is fundamentally driven by the intricate interplay of molecular pathways and regulatory mechanisms within cells and tissues. Understanding these pathways, their components, interactions, and functional significance is crucial for elucidating disease etiology and identifying potential therapeutic interventions. Progression often involves dysregulation across multiple integrated biological networks.
Cellular Signaling and Transcriptional Regulation
Cellular signaling pathways are critical for transmitting information from the extracellular environment to the cell's interior, orchestrating responses that impact cell growth, differentiation, and survival. Receptor activation initiates intracellular signaling cascades, such as the phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) pathways, which can be mediated by presenilins through select signaling receptors. [25] Similarly, BCR-mediated signal transduction plays a role in B cell function. [34] The mitogen-activated protein kinase (MAPK) pathway is another crucial cascade, regulated by protein families like Tribbles, which control its activation and downstream effects. [35]
These signaling cascades frequently converge on the regulation of transcription factors, which in turn control gene expression. For example, TGF-beta signaling, mediated by Smad proteins, involves Smad3 allosteric control that links receptor kinase activation directly to transcriptional changes. [36] Dysregulation of transcription factors, such as the elevation of CCAAT/Enhancer binding protein δ (C/EBP-δ) expression in Alzheimer’s disease, can significantly alter gene expression profiles relevant to disease pathology. [37] Furthermore, factors like SREBP-2 are known to regulate metabolic genes, demonstrating how signaling pathways integrate with transcriptional control to influence fundamental cellular processes like lipid metabolism. [38]
Metabolic Control and Bioenergetics
Metabolic pathways are central to energy production, biosynthesis, and catabolism, with their dysregulation profoundly influencing disease progression. Energy metabolism, for instance, is influenced by genes like SIRT3, whose variability has been associated with survivorship in the elderly. [39] The highly conserved insulin/IGF-1 signaling pathway also plays a critical role in metabolic regulation, with reduced activity linked to human longevity. [40] These pathways govern how cells utilize nutrients and maintain energetic balance, and their disruption can contribute to age-related pathologies and metabolic disorders.
Specific metabolic transporters and enzymes are also crucial in maintaining metabolic homeostasis. The SLC2A9 (GLUT9) gene, a member of the facilitative glucose transporter family, functions as a renal urate anion exchanger and significantly influences serum uric acid levels and excretion. [41] Dysregulation of this transporter can lead to conditions like gout. In lipid metabolism, proteins such as ANGPTL3 and ANGPTL4 regulate lipid concentrations, with variations in ANGPTL4 affecting triglyceride levels and HDL cholesterol. [42] Additionally, enzymes like glutathione S-transferase omega 1 and 2 are involved in detoxification and catabolism, highlighting the diverse roles of metabolic pathways in cellular health and disease. [43]
Protein Homeostasis and Post-Translational Modification
Maintaining protein homeostasis, including proper folding, modification, and degradation, is essential for cellular function, and its disruption is a hallmark of many diseases. Post-translational modifications, such as phosphorylation, are key regulatory mechanisms; for example, the phosphorylation of Heat Shock Protein-90 (HSP90) by TSH demonstrates how hormonal signals can modulate protein activity and stability. [44] Similarly, the Tribbles protein family regulates MAPK cascades through various modifications, impacting cell signaling and proliferation. [35] These modifications allow for rapid and reversible control of protein function in response to cellular needs.
The ubiquitin-proteasome system is a primary pathway for targeted protein degradation, crucial for removing misfolded or damaged proteins and regulating protein turnover. In neurodegenerative disorders like Parkinson’s disease, mutations in genes such as parkin, which encodes an E3 ubiquitin ligase, disrupt this pathway, leading to the accumulation of aberrant proteins and neuronal damage. [45] The identification of other ubiquitin ligases like PJA1 further underscores the importance of this system in maintaining protein quality control and its relevance to disease pathology. [46]
Integrated Network Dysregulation in Disease Progression
Biological systems operate through highly interconnected networks where pathways constantly crosstalk, leading to emergent properties that dictate cellular and organismal health. Pathway crosstalk is evident in conditions like atherosclerosis, where impaired TGF-beta/Smad signaling in smooth muscle cells of fibrofatty lesions contributes to disease progression. [47] Similarly, in cardiovascular physiology, angiotensin II can antagonize cGMP signaling by increasing phosphodiesterase 5A (PDE5A) expression in vascular smooth muscle cells, illustrating a molecular mechanism of pathway interaction. [48] The CFTR chloride channel also exemplifies network integration by altering mechanical properties and cAMP-dependent Cl- transport in endothelial cells, impacting vascular function. [28]
Understanding disease progression often requires a systems-level approach, as complex traits and common diseases arise from the dysregulation of multiple interacting pathways. Genome-wide association studies have been instrumental in identifying networks of disease susceptibility genes, revealing how diverse biochemical pathways can converge on common pathophysiological mechanisms. [4] For instance, in Crohn's disease, susceptibility genes point to converging pathways central to epithelial defense, innate and adaptive immune responses, and tissue repair. [4] Furthermore, genetic modifiers, such as GAB2 alleles modifying Alzheimer's risk in APOE epsilon4 carriers, demonstrate hierarchical regulation and the complex genetic architecture underlying disease susceptibility and progression. [16]
Prognostic Indicators and Risk Stratification
Genetic research plays a crucial role in identifying prognostic indicators for disease progression and enabling effective risk stratification. Studies aim to uncover biomarkers that contribute to early disease detection and primary prevention strategies, particularly for complex conditions such as Parkinson's disease. Such insights can also nominate new molecular targets for disease-modifying therapies, facilitating secondary prevention. [3] The ability to predict treatment effects based on an individual's genotype, sometimes conceptualized as "virtual clinical trials," holds promise for reducing research costs and identifying patient subgroups most likely to benefit from specific interventions, thereby advancing personalized medicine. [3] For age-related conditions like cardiovascular disease, dementia, and cancer, genetic factors can influence morbidity-free survival, highlighting their importance in assessing long-term health outcomes and guiding prevention efforts. [11] Similarly, for pulmonary conditions, genetic correlates can be identified for the annual rate of decline in measures such as FEV1 and FVC, providing objective data on disease progression and long-term prognosis. [12] In diabetes, specific single nucleotide polymorphisms (SNPs) have been associated with diabetes survival, offering potential prognostic markers for the disease course. [6] Furthermore, alleles of genes like GAB2 have been shown to modify the risk of Alzheimer's disease in individuals carrying APOE epsilon4, providing crucial information for risk stratification and early intervention strategies in high-risk populations. [16]
Clinical Applications and Monitoring Strategies
Genetic findings translate into practical clinical applications through improved diagnostic utility and refined monitoring strategies. Genome-wide association studies (GWAS) contribute to diagnostic utility by identifying novel disease genes, such as NELL1 in Inflammatory Bowel Disease (IBD), which can deepen the understanding of disease mechanisms and potentially lead to new diagnostic markers. [1] The identification of protein quantitative trait loci (pQTLs) suggests that genetic variants can influence protein levels, providing potential circulating biomarkers for monitoring disease activity or treatment response. [14] For example, associations between polymorphisms in the HNF1A gene and C-reactive protein (CRP) levels highlight a genetic influence on this key inflammatory biomarker, which is widely used in monitoring various inflammatory and cardiovascular conditions, though CRP levels can also be influenced by treatments like statins. [49] Beyond inflammation, biomarkers such as MCP1 and B-type natriuretic peptide (BNP) have been associated with specific genetic variants, offering further avenues for risk assessment and monitoring of cardiovascular health. [13] In cardiovascular diseases, genetic associations with echocardiographic dimensions, such as left ventricular diastolic and systolic diameters, and brachial artery endothelial function, can provide objective measures for monitoring disease progression and assessing treatment efficacy. [5] These findings support a personalized medicine approach, where genetic profiles can guide treatment selection, ensuring patients receive therapies most likely to be effective while avoiding those with potential for limited benefit or adverse effects. [3]
Genetic Associations and Comorbidities
Understanding disease progression also necessitates recognizing overlapping phenotypes and comorbidities. Studies, such as those within the Framingham Heart Study, have explored genetic correlates of morbidity-free survival, specifically considering freedom from cardiovascular disease (CVD), dementia, and cancer as key endpoints, highlighting the interrelation of these age-related conditions. [11] The progression of conditions like nephropathy in type 2 diabetes exemplifies how one chronic disease can lead to severe complications, with research focusing on factors like blood pressure control and proteinuria as crucial elements in managing renal disease progression. [10] Genetic pleiotropy, where a single genetic variant influences multiple traits or diseases, is an important consideration in understanding complex disease associations and potential shared underlying mechanisms. [13] Furthermore, research into cardiovascular disease outcomes often accounts for comorbidities such as diabetes, systolic blood pressure, and valve disease as covariates, demonstrating the clinical necessity of considering the full patient profile when assessing genetic risk and disease progression . The identification of novel disease genes, such as NELL1 in Inflammatory Bowel Disease, alongside established associations like NOD2 in Crohn's disease, contributes to a more complete picture of disease pathogenesis and its potential links to other inflammatory conditions. [1]
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs2284665 | HTRA1 | disease progression measurement laterality measurement stroke age-related macular degeneration Blindness |
| rs10733086 | CFH | disease progression measurement |
| rs182987047 | RIMS2 | disease progression measurement |
| rs429358 | APOE | cerebral amyloid deposition measurement Lewy body dementia, Lewy body dementia measurement high density lipoprotein cholesterol measurement platelet count neuroimaging measurement |
| rs150468541 | IQCJ, IQCJ-SCHIP1 | disease progression measurement |
| rs1404610 | LINC01101 - Y_RNA | disease progression measurement |
| rs2327990 | MACROD2 - PPIAP17 | disease progression measurement |
| rs2366964 | FHIT | disease progression measurement |
| rs11918092 | RNA5SP141 - EPHB1 | disease progression measurement |
| rs9534678 | RN7SL700P - SUCLA2 | disease progression measurement |
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