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Journal of the American Society of... Apr 2020
Topics: Calmodulin-Binding Proteins; Genetic Predisposition to Disease; Homeostasis; Humans; Mutation; Renal Circulation
PubMed: 32123053
DOI: 10.1681/ASN.2020020139 -
Clinical Genetics Aug 2013Refractive errors, myopia and hyperopia, are the most common causes of visual impairment worldwide. Recent advances in genetics have been utilized to identify a wealth... (Review)
Review
Refractive errors, myopia and hyperopia, are the most common causes of visual impairment worldwide. Recent advances in genetics have been utilized to identify a wealth of genetic loci believed to contain susceptibility genes for refractive error (RE). The current genetic evidence confirms that RE is influenced by both common and rare variants with a significant environmental component. These studies argue that only by combining genetic and environmental knowledge with in vivo measurements of biological states will it be possible to understand the underlying biology of RE that will lead to novel therapeutic targets and accurate genetic predictions.
Topics: Animals; Disease Models, Animal; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Humans; Phenotype; Refractive Errors
PubMed: 23647423
DOI: 10.1111/cge.12180 -
Discovery Medicine Aug 2010Systemic sclerosis (SSc, scleroderma) is an autoimmune disease clinically characterized by progressive fibrosis in the skin and internal organs. While the pathogenesis... (Review)
Review
Systemic sclerosis (SSc, scleroderma) is an autoimmune disease clinically characterized by progressive fibrosis in the skin and internal organs. While the pathogenesis of SSc is not completely understood, familial studies and genetic studies suggest that SSc is a complex polygenic disease. In the current review, we will discuss recent studies investigating genetic susceptibility to SSc. Candidate gene studies have identified critical immunoregulatory genes and gene regions including BANK1, FAM167A-BLK, IL23R, IRF5, STAT4, TBX21, and TNFSF4 as susceptibility genes for the development of SSc. More recently a genome-wide association study has been performed and identified CD247 (CD3-zeta) as a novel genetic risk factor for the susceptibility to SSc. Together these genetic association studies have substantially advanced our understanding of SSc pathogenesis and form the foundation for future studies seeking to understand the complexities of SSc.
Topics: Family; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA Antigens; Humans; Scleroderma, Systemic
PubMed: 20807474
DOI: No ID Found -
International Journal of Environmental... Apr 2013The arsenic (As) exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic,... (Review)
Review
The arsenic (As) exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic-health effects.
Topics: Arsenic; DNA Damage; Environmental Pollutants; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic
PubMed: 23583964
DOI: 10.3390/ijerph10041527 -
Journal of Neuroimmune Pharmacology :... Dec 2018The clinical translation of genetic research on nicotine dependence and treatment response requires acceptance of genetic testing by smokers. This study determines (1)... (Observational Study)
Observational Study Randomized Controlled Trial
The clinical translation of genetic research on nicotine dependence and treatment response requires acceptance of genetic testing by smokers. This study determines (1) which current smokers are receptive to genetic susceptibility testing for nicotine dependence and (2) to what potential extent smokers motivated to quit desire to take smoking cessation medication when hypothetical genetic results predict their pharmacogenetic medication response. Current smokers from a genetic nicotine dependence study (n = 1306) and an ongoing smoking cessation trial (n = 209) were surveyed on their hypothetical interest in seeing genetic testing results related to risk of nicotine dependence. Most current smokers (84.8%) reported high interest in receiving genetic testing results. Factors associated with high interest included age ≥ 40 years, having a college degree, and a positive medical history (≥1 medical condition). In the ongoing smoking cessation trial, current smokers motivated to quit (n = 474) were surveyed on their desire to take smoking cessation medication given hypothetical below or above average pharmacogenetic responses to the medication. When the hypothetical medication response changed from below to above average, significantly more smokers reported a desire to take medication (from 61.0% to 97.5%, p < .0001). These preliminary findings suggest that genetic testing for personalized smoking cessation treatment is well-received by smokers and that a positive hypothetical pharmacogenetic response increases desire to take smoking cessation medication among current smokers motivated to quit. Graphical abstract ᅟ.
Topics: Adult; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Male; Middle Aged; Smokers; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 30370503
DOI: 10.1007/s11481-018-9818-1 -
Frontiers in Public Health 2023Observational studies have revealed that socioeconomic status is associated with neurological disorders and aging. However, the potential causal effect between the two...
Exploring the bidirectional causal link between household income status and genetic susceptibility to neurological diseases: findings from a Mendelian randomization study.
OBJECTIVES
Observational studies have revealed that socioeconomic status is associated with neurological disorders and aging. However, the potential causal effect between the two remains unclear. We therefore aimed to investigate the causal relationship between household income status and genetic susceptibility to neurological diseases using a bidirectional Mendelian randomization (MR) study.
METHODS
An MR study was conducted on a large-sample cohort of the European population pulled from a publicly available genome-wide association study dataset, using a random-effects inverse-variance weighting model as the main standard. MR-Egger regression, weighted median, and maximum likelihood estimation were also performed concurrently as supplements. A sensitivity analysis, consisting of a heterogeneity test and horizontal pleiotropy test, was performed using Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of the conclusion.
RESULTS
The results suggested that higher household income tended to lower the risk of genetic susceptibility to Alzheimer's disease (odds ratio [OR]: 0.740, 95% confidence interval [CI] = 0.559-0.980, -value = 0.036) and ischemic stroke (OR: 0.801, 95% CI = 0.662-0.968, -value = 0.022). By contrast, higher household income tended to increase the risk of genetic susceptibility to Parkinson's disease (OR: 2.605, 95% CI = 1.413-4.802, -value = 0.002). No associations were evident for intracranial hemorrhage (OR: 1.002, 95% CI = 0.607-1.653, -value = 0.993), cerebral aneurysm (OR: 0.597, 95% CI = 0.243-1.465, -value = 0.260), subarachnoid hemorrhage (OR: 1.474, 95% CI = 0.699-3.110, -value = 0.308), or epilepsy (OR: 1.029, 95% CI = 0.662-1.600, -value = 0.899). The reverse MR study suggested no reverse causal relationship between neurological disorders and household income status. A sensitivity analysis verified the reliability of the results.
CONCLUSION
Our results revealed that the populations with a superior household income exhibit an increased predisposition of genetic susceptibility to Parkinson's Disease, while demonstrating a potential decreased genetic susceptibility to ischemic stroke and Alzheimer's disease.
Topics: Humans; Genetic Predisposition to Disease; Parkinson Disease; Alzheimer Disease; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Nervous System Diseases; Ischemic Stroke
PubMed: 37564429
DOI: 10.3389/fpubh.2023.1202747 -
Environment International Mar 2018More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many... (Review)
Review
More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many diseases, including cancer. Epidemiological evidence supports its carcinogenic potential, however, detailed molecular mechanisms remain to be elucidated. Despite the global magnitude of this problem, not all individuals face the same risk. Susceptibility to the toxic effects of arsenic is influenced by alterations in genes involved in arsenic metabolism, as well as biological factors, such as age, gender and nutrition. Moreover, chronic arsenic exposure results in several genotoxic and epigenetic alterations tightly associated with the arsenic biotransformation process, resulting in an increased cancer risk. In this review, we: 1) review the roles of inter-individual DNA-level variations influencing the susceptibility to arsenic-induced carcinogenesis; 2) discuss the contribution of arsenic biotransformation to cancer initiation; 3) provide insights into emerging research areas and the challenges in the field; and 4) compile a resource of publicly available arsenic-related DNA-level variations, transcriptome and methylation data. Understanding the molecular mechanisms of arsenic exposure and its subsequent health effects will support efforts to reduce the worldwide health burden and encourage the development of strategies for managing arsenic-related diseases in the era of personalized medicine.
Topics: Animals; Arsenic; Environmental Exposure; Genetic Predisposition to Disease; Humans; Water Pollutants, Chemical
PubMed: 29275244
DOI: 10.1016/j.envint.2017.12.017 -
Radiation Research Jul 2022Previous epidemiological studies have demonstrated elevated susceptibility to ionizing radiation in some families, thus suggesting the presence of genetic components...
Previous epidemiological studies have demonstrated elevated susceptibility to ionizing radiation in some families, thus suggesting the presence of genetic components that conferred increased rate of radiation-associated meningioma (RAM). In this study, we exome-sequenced and investigated the segregation pattern of rare deleterious variants in 11 RAM pedigrees. In addition, we performed a rare-variant association analysis in 92 unrelated familial cases of RAM that were ancestry-matched with 88 meningioma-free controls. In the pedigree analysis, we found that each family carried mostly a unique set of rare deleterious variants. A follow-up pathway analysis of the union of the genes that segregated within each of the 11 pedigrees identified a single statistically significant (q value = 7.90E-04) "ECM receptor interaction" set. In the case-control association analysis, we observed no statistically significant variants or genes after multiple testing correction; however, examination of ontological categories of the genes that associated with RAM at nominal P values <0.01 identified biologically relevant pathways such as DNA repair, cell cycle and apoptosis. These results suggest that it is unlikely that a small number of highly penetrant genes are involved in the pathogenesis of RAM. Substantially larger studies are needed to identify genetic risk variants and genes in RAM.
Topics: Case-Control Studies; Exome; Genetic Predisposition to Disease; Humans; Pedigree; Radiation, Ionizing
PubMed: 35405740
DOI: 10.1667/RADE-21-00035.1 -
Immunogenetics Aug 2022COVID-19 is a new complex multisystem disease caused by the novel coronavirus SARS-CoV-2. In slightly over 2 years, it infected nearly 500 million and killed 6 million... (Review)
Review
COVID-19 is a new complex multisystem disease caused by the novel coronavirus SARS-CoV-2. In slightly over 2 years, it infected nearly 500 million and killed 6 million human beings worldwide, causing an unprecedented coronavirus pandemic. Currently, the international scientific community is engaged in elucidating the molecular mechanisms of the pathophysiology of SARS-CoV-2 infection as a basis of scientific developments for the future control of COVID-19. Global exome and genome analysis efforts work to define the human genetics of protective immunity to SARS-CoV-2 infection. Here, we review the current knowledge regarding the SARS-CoV-2 infection, the implications of COVID-19 to Public Health and discuss genotype to phenotype association approaches that could be exploited through the selection of candidate genes to identify the genetic determinants of severe COVID-19.
Topics: COVID-19; Genetic Predisposition to Disease; Humans; Pandemics; Public Health; SARS-CoV-2
PubMed: 35348847
DOI: 10.1007/s00251-022-01261-w -
Endocrine Reviews Oct 2008Type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) frequently occur together within families and in the same individual. The co-occurrence of T1D and AITD in... (Review)
Review
Type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) frequently occur together within families and in the same individual. The co-occurrence of T1D and AITD in the same patient is one of the variants of the autoimmune polyglandular syndrome type 3 [APS3 variant (APS3v)]. Epidemiological data point to a strong genetic influence on the shared susceptibility to T1D and AITD. Recently, significant progress has been made in our understanding of the genetic association between T1D and AITD. At least three genes have been confirmed as major joint susceptibility genes for T1D and AITD: human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22. Moreover, the first whole genome linkage study has been recently completed, and additional genes will soon be identified. Not unexpectedly, all the joint genes for T1D and AITD identified so far are involved in immune regulation, specifically in the presentation of antigenic peptides to T cells. One of the lessons learned from the analysis of the joint susceptibility genes for T1D and AITD is that subset analysis is a key to dissecting the etiology of complex diseases. One of the best demonstrations of the power of subset analysis is the CTLA-4 gene in T1D. Although CTLA-4 showed very weak association with T1D, when analyzed in the subset of patients with both T1D and AITD, the genetic effect of CTLA-4 was significantly stronger. Gene-gene and genetic-epigenetic interactions most likely play a role in the shared genetic susceptibility to T1D and AITD. Dissecting these mechanisms will lead to a better understanding of the etiology of T1D and AITD, as well as autoimmunity in general.
Topics: Diabetes Mellitus, Type 1; Genetic Predisposition to Disease; Humans; Thyroiditis, Autoimmune
PubMed: 18776148
DOI: 10.1210/er.2008-0015