scholarly journals How to identify gene–environment interactions in a multifactorial disease: CHD as an example

2004 ◽  
Vol 63 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Philippa J. Talmud
Keyword(s):  
Environmental Factors ◽  
Context Dependency ◽  
Single Mutation ◽  
Small Contribution ◽  
Multifactorial Disease ◽  
Risk Environment ◽  
Chd Risk ◽  
Gene Environment ◽  
E4 Allele ◽  
The Impact

CHD is a multifactorial disease, caused by both genetic and environmental factors. The inherited 'defective' genes will vary from individual to individual, and any single mutation is likely to be making only a small contribution to risk. The context dependency, i.e. the importance of environmental factors in influencing genetic risk, is now becoming evident. Thus, a mutation may have a modest effect on risk in individuals who maintain a low environmental risk, but a major effect in a high-risk environment. Methods of analysing gene–environment interactions on CHD risk will be discussed and illustrated with several examples. APOE has three common alleles, ɛ2, ɛ3 and ɛ4. The ɛ4 allele has consistently been associated with CHD risk, which has been confirmed by meta-analysis. However, when the effect of genotype on risk was considered in smokers and non-smokers separately, risk in non-smokers was similar in all APOE genotypes. By comparison, in the smokers, ɛ3 homozygotes, as expected, had an approximately 2-fold higher risk, while for ɛ4 carriers there was a significantly greater than additive effect of genotype and smoking on risk (P ≫0.007). Thus, the impact of the ɛ4 allele on CHD risk appears to be confined to current smokers, an effect that has been confirmed in several studies. Another example is the interaction between the alcohol dehydrogenase 3 gene variant and alcohol consumption on CHD risk (P ≫0.001), showing the context dependency of the effect. Thus, the importance of considering environmental factors as potential genotype-risk modifiers has major public health implications.

scholarly journals Impacts of Environmental Factors on Head and Neck Cancer Pathogenesis and Progression

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 389
Author(s):  
Marisol Miranda-Galvis ◽  
Reid Loveless ◽  
Luiz Paulo Kowalski ◽  
Yong Teng
Keyword(s):  
Head And Neck Cancer ◽  
Environmental Factors ◽  
Head And Neck ◽  
Neck Cancer ◽  
Molecular Mechanisms ◽  
Metastatic Cancer ◽  
Environmental Drivers ◽  
Cancer Pathogenesis ◽  
Gene Environment ◽  
The Impact

Epidemiological and clinical studies over the past two decades have provided strong evidence that genetic elements interacting with environmental components can individually and collectively influence one’s susceptibility to cancer. In addition to tumorigenic properties, numerous environmental factors, such as nutrition, chemical carcinogens, and tobacco/alcohol consumption, possess pro-invasive and pro-metastatic cancer features. In contrast to traditional cancer treatment, modern therapeutics not only take into account an individual’s genetic makeup but also consider gene–environment interactions. The current review sharpens the focus by elaborating on the impact that environmental factors have on the pathogenesis and progression of head and neck cancer and the underlying molecular mechanisms involved. Recent advances, challenges, and future perspectives in this area of research are also discussed. Inhibiting key environmental drivers of tumor progression should yield survival benefits for patients at any stage of head and neck cancer.

Gene–environment interplay in the etiology of psychosis

2018 ◽  
Vol 48 (12) ◽  
pp. 1925-1936 ◽  
Author(s):  
Alyson Zwicker ◽  
Eileen M. Denovan-Wright ◽  
Rudolf Uher
Keyword(s):  
Environmental Factors ◽  
Genetic Risk ◽  
Environmental Exposures ◽  
Response To Treatment ◽  
Human Potential ◽  
Specific Gene ◽  
Environment Interaction ◽  
Gene Environment ◽  
Increased Risk ◽  
The Impact

AbstractSchizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene–environment interactions. Only a few specific gene–environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene–environment interaction is a common polymorphism in theAKT1gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

scholarly journals The Impact of Environmental Factors on Monogenic Mendelian Diseases

2021 ◽  
Author(s):  
Anke M Tukker ◽  
Charmaine D Royal ◽  
Aaron B Bowman ◽  
Kimberly A McAllister
Keyword(s):  
Environmental Factors ◽  
Complex Disease ◽  
Health Science ◽  
Model Systems ◽  
Mendelian Disease ◽  
Disease Etiology ◽  
Mendelian Disorders ◽  
Mendelian Diseases ◽  
Gene Environment ◽  
The Impact

Abstract Environmental factors and gene-environment interactions modify the variable expressivity, progression, severity, and onset of some classic (monogenic) Mendelian-inherited genetic diseases. Cystic fibrosis, Huntington disease, Parkinson’s disease, and sickle cell disease are examples of well-known Mendelian disorders that are influenced by exogenous exposures. Environmental factors may act by direct or indirect mechanisms to modify disease severity, timing, and presentation, including through epigenomic influences, protein misfolding, miRNA alterations, transporter activity, and mitochondrial effects. Because pathological features of early-onset Mendelian diseases can mimic later onset complex diseases, we propose that studies of environmental exposure vulnerabilities using monogenic model systems of rare Mendelian diseases have high potential to provide insight into complex disease phenotypes arising from multi-genetic/multi-toxicant interactions. Mendelian disorders can be modeled by homologous mutations in animal model systems with strong recapitulation of human disease etiology and natural history, providing an important advantage for study of these diseases. Monogenic high penetrant mutations are ideal for toxicant challenge studies with a wide variety of environmental stressors, because background genetic variability may be less able to alter the relatively strong phenotype driving disease-causing mutations. These models promote mechanistic understandings of gene-environment interactions and biological pathways relevant to both Mendelian and related sporadic complex disease outcomes by creating a sensitized background for relevant environmental risk factors. Additionally, rare disease communities are motivated research participants, creating the potential of strong research allies among rare Mendelian disease advocacy groups and disease registries and providing a variety of translational opportunities that are under-utilized in genetic or environmental health science.

scholarly journals Impact of Gene–Environment Interactions on Cancer Development

2020 ◽  
Vol 17 (21) ◽  
pp. 8089
Author(s):  
Ariane Mbemi ◽  
Sunali Khanna ◽  
Sylvianne Njiki ◽  
Clement G. Yedjou ◽  
Paul B. Tchounwou
Keyword(s):  
Environmental Factors ◽  
Scientific Evidence ◽  
Critical Role ◽  
Experimental Studies ◽  
Joint Effect ◽  
Human Diseases ◽  
Nucleotide Polymorphisms ◽  
Gene Environment ◽  
Genetic And Environmental Factors ◽  
The Impact

Several epidemiological and experimental studies have demonstrated that many human diseases are not only caused by specific genetic and environmental factors but also by gene–environment interactions. Although it has been widely reported that genetic polymorphisms play a critical role in human susceptibility to cancer and other chronic disease conditions, many single nucleotide polymorphisms (SNPs) are caused by somatic mutations resulting from human exposure to environmental stressors. Scientific evidence suggests that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Research has also pointed out that the interactions of environmental factors with specific allelic variants highly modulate the susceptibility to diseases. Hence, many scientific discoveries on gene–environment interactions have elucidated the impact of their combined effect on the incidence and/or prevalence rate of human diseases. In this review, we provide an overview of the nature of gene–environment interactions, and discuss their role in human cancers, with special emphases on lung, colorectal, bladder, breast, ovarian, and prostate cancers.

A model of neurocognitive function in spina bifida over the life span

2006 ◽  
Vol 12 (2) ◽  
pp. 285-296 ◽  
Author(s):  
MAUREEN DENNIS ◽  
SUSAN H. LANDRY ◽  
MARCIA BARNES ◽  
JACK M. FLETCHER
Keyword(s):  
Environmental Factors ◽  
Spina Bifida ◽  
Movement Timing ◽  
Associative Processing ◽  
Domain Specific ◽  
Cognitive Phenotype ◽  
Naturally Occurring ◽  
Gene Environment ◽  
Environmental Events ◽  
The Impact

Spina bifida myelomeningocele (SBM), a neural tube defect that is the product of a complex pattern of gene-environment interactions, is associated with naturally occurring, systematic variability in the neural phenotype and in environmental factors that lead to systematic variability in the cognitive phenotype. We characterize the basis for variability in the cognitive phenotype of children with SBM with reference to a model of key biological, cognitive, and environmental events unfolding over the course of development from infancy to middle age. The cognitive phenotype is not domain-specific, but represents manifestations of unobservable constructs involving associative and assembled processing, the latter directly reflecting the impact of the neural phenotype on core deficits involving movement, timing, and attention orienting. The expression of the cognitive phenotype is variable, being moderated by features of the neural phenotype involving secondary CNS insults (such as hydrocephalus) that impair assembled processing, as well as by environmental factors (such as poverty, parenting, and education) that impair associative processing. The preservation of strengths in associative processing depends in part on the severity of the CNS deficits in SBM and the impact of the environment. (JINS, 2006, 12, 285–296.)

Assessing the sustainability of the Siberian Federal District regions

2020 ◽  
Vol 18 (5) ◽  
pp. 891-908
Author(s):  
T.A. Smirnova
Keyword(s):  
Sustainable Development ◽  
Environmental Factors ◽  
Regional Development ◽  
Federal District ◽  
Integrated Approach ◽  
Siberian Federal District ◽  
The Sustainable Development ◽  
The Impact ◽  
Empirical Analyses

Subject. This article deals with the issues of functioning of the region as a system. Objectives. The article aims to identify the problems of the region's functioning as a system, develop methodological tools to monitor the sustainable development of the Siberian Federal District territories, and determine the the impact of socio-economic and environmental factors on the sustainable development of the region as a whole. Methods. For the study, I used the methods of theoretical, statistical, and empirical analyses taking into account an integrated approach. Results. The article reveals the impact of some individual components of regional development on the sustainability of the territorial system as a whole. Relevance. The results of the study can be used to analyze the sustainability of regions' development.

Directions of Accounting Environmental Factors for Forecasting Formation of Agroecosystems

2020 ◽  
pp. 31-35
Author(s):  
L.Z. Khalishkhova ◽  
◽  
A. Kh. Temrokova ◽  
I.R. Guchapsheva ◽  
K.A. Bogаtyreva ◽  
...  
Keyword(s):  
Sustainable Development ◽  
Comparative Analysis ◽  
Environmental Factors ◽  
Environmental Safety ◽  
Logical Analysis ◽  
Management Decisions ◽  
The Sustainable Development ◽  
The Impact

Ensuring the sustainable development of agroecosystems requires research into the justification of the impact of environmental factors on the formation of territorial agroecosystems and identifies ways to take them into account in order to justify management decisions and ensure environmental safety. The main goal of the research within the article is to identify the most significant environmental factors in predicting the formation of agroecosystems. Provisions are devoted to the study of the laws governing the functioning of agroecosystems in order to increase their stability. The methods of comparative analysis, generalization, abstraction, logical analysis are applied. A number of provisions are formulated regarding ways to account for the influence of factors on the formation of key elements of agroecosystems.

scholarly journals GPS Coordinates for Modelling Correlated Herd Effects in Genomic Prediction Models Applied to Hanwoo Beef Cattle

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2050
Author(s):  
Beatriz Castro Dias Cuyabano ◽  
Gabriel Rovere ◽  
Dajeong Lim ◽  
Tae Hun Kim ◽  
Hak Kyo Lee ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Genomic Prediction ◽  
Prediction Models ◽  
Phenotypic Expression ◽  
Genetic Evaluation ◽  
Genomic Breeding ◽  
Breeding Values ◽  
Korean Cattle ◽  
Evaluation Programs ◽  
The Impact

It is widely known that the environment influences phenotypic expression and that its effects must be accounted for in genetic evaluation programs. The most used method to account for environmental effects is to add herd and contemporary group to the model. Although generally informative, the herd effect treats different farms as independent units. However, if two farms are located physically close to each other, they potentially share correlated environmental factors. We introduce a method to model herd effects that uses the physical distances between farms based on the Global Positioning System (GPS) coordinates as a proxy for the correlation matrix of these effects that aims to account for similarities and differences between farms due to environmental factors. A population of Hanwoo Korean cattle was used to evaluate the impact of modelling herd effects as correlated, in comparison to assuming the farms as completely independent units, on the variance components and genomic prediction. The main result was an increase in the reliabilities of the predicted genomic breeding values compared to reliabilities obtained with traditional models (across four traits evaluated, reliabilities of prediction presented increases that ranged from 0.05 ± 0.01 to 0.33 ± 0.03), suggesting that these models may overestimate heritabilities. Although little to no significant gain was obtained in phenotypic prediction, the increased reliability of the predicted genomic breeding values is of practical relevance for genetic evaluation programs.

scholarly journals Are Bacterio- and Phytoplankton Community Compositions Related in Lakes Differing in Their Cyanobacteria Contribution and Physico-Chemical Properties?

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 855
Author(s):  
Mikołaj Kokociński ◽  
Dariusz Dziga ◽  
Adam Antosiak ◽  
Janne Soininen
Keyword(s):  
Environmental Factors ◽  
Community Composition ◽  
Phytoplankton Community ◽  
Heterotrophic Bacteria ◽  
Bacterial Community Composition ◽  
Physical Factors ◽  
Research Attention ◽  
Phytoplankton Community Composition ◽  
The Impact ◽  
Bacteria Communities

Bacterioplankton community composition has become the center of research attention in recent years. Bacteria associated with toxic cyanobacteria blooms have attracted considerable interest. However, little is known about the environmental factors driving the bacteria community, including the impact of invasive cyanobacteria. Therefore, our aim has been to determine the relationships between heterotrophic bacteria and phytoplankton community composition across 24 Polish lakes with different contributions of cyanobacteria including the invasive species Raphidiopsis raciborskii. This analysis revealed that cyanobacteria were present in 16 lakes, while R. raciborskii occurred in 14 lakes. Our results show that bacteria communities differed between lakes dominated by cyanobacteria and lakes with minor contributions of cyanobacteria but did not differ between lakes with R. raciborskii and other lakes. Physical factors, including water and Secchi depth, were the major drivers of bacteria and phytoplankton community composition. However, in lakes dominated by cyanobacteria, bacterial community composition was also influenced by biotic factors such as the amount of R. raciborskii, chlorophyll-a and total phytoplankton biomass. Thus, our study provides novel evidence on the influence of environmental factors and R. raciborskii on lake bacteria communities.

scholarly journals Enhanced Viral Activity in the Surface Microlayer of the Arctic and Antarctic Oceans

2021 ◽  
Vol 9 (2) ◽  
pp. 317
Author(s):  
Dolors Vaqué ◽  
Julia A. Boras ◽  
Jesús Maria Arrieta ◽  
Susana Agustí ◽  
Carlos M. Duarte ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Food Web ◽  
Physicochemical Characteristics ◽  
The Arctic ◽  
Microbial Food Web ◽  
Surface Microlayer ◽  
Polar Regions ◽  
Nutrient Inputs ◽  
Viral Activity ◽  
The Impact

The ocean surface microlayer (SML), with physicochemical characteristics different from those of subsurface waters (SSW), results in dense and active viral and microbial communities that may favor virus–host interactions. Conversely, wind speed and/or UV radiation could adversely affect virus infection. Furthermore, in polar regions, organic and inorganic nutrient inputs from melting ice may increase microbial activity in the SML. Since the role of viruses in the microbial food web of the SML is poorly understood in polar oceans, we aimed to study the impact of viruses on prokaryotic communities in the SML and in the SSW in Arctic and Antarctic waters. We hypothesized that a higher viral activity in the SML than in the SSW in both polar systems would be observed. We measured viral and prokaryote abundances, virus-mediated mortality on prokaryotes, heterotrophic and phototrophic nanoflagellate abundance, and environmental factors. In both polar zones, we found small differences in environmental factors between the SML and the SSW. In contrast, despite the adverse effect of wind, viral and prokaryote abundances and virus-mediated mortality on prokaryotes were higher in the SML than in the SSW. As a consequence, the higher carbon flux released by lysed cells in the SML than in the SSW would increase the pool of dissolved organic carbon (DOC) and be rapidly used by other prokaryotes to grow (the viral shunt). Thus, our results suggest that viral activity greatly contributes to the functioning of the microbial food web in the SML, which could influence the biogeochemical cycles of the water column.

Sign in / Sign up

Export Citation Format

Share Document