Gene-Environment Interactions Quiz

Gene-Environment Interactions (GEIs)

• GEIs occur when environmental factors (e.g., diet, pollution) interact with genes, affecting disease risk.
• Exposure to pollution can increase asthma risk, but genetics influence the extent of the impact.
• GEI studies primarily focus on the interaction between genetics and environmental exposures in impacting health.
• GEIs have varying effects across different life stages (e.g., prenatal and early childhood development).
• This stage significantly influences gene regulation and disease risk, for example, prenatal exposure to certain toxins.

GEI Lecture Outline

• Introduction to the Field of GEI
• Advantages and Challenges in GEI Analysis
• Integration of Multi-omics Data
• Clinical Applications of GEI Research
• Social Impacts of GEI Research
• GEI within the Precision Environmental Health (PEH) Framework

Introduction

• Key Focus: Exploring the complex interaction of genetic and environmental factors in disease development.
• Key Concepts: Importance of GEIs in disease etiology, and overview of development-stage impacts of GEIs.

Precision Environmental Health (PEH)

• Omics and exposure data across the life course are used in PEH.
• Machine learning, mass spectrometry, and omics technologies are key aspects.
• Risk identification and precision health intervention.

What are Gene-Environment Interactions (GEIs)?

• GEIs happen when the environment (e.g., diet, air) interacts with genes, influencing disease risk.

Gene-Environment Interactions (GEI) Overview

• Examples: BRCA-1 mutation and asbestos exposure (mesothelioma); DRD4 gene and parenting style (ADHD).
• Definition: A GEI occurs when environmental exposure impacts disease risk based on individual genetic makeup.

Precision Environmental Health: Use of Omics and Exposures Retrospectively

• Omic data (e.g., genomics, epigenomics, metabolomics, transcriptomics) and exposure data are utilized (e.g., medications, exercise, stress, diet, domicile, occupational factors, environmental factors).
• Feature selection (statistical learning, elastic net, ridge regression, neural nets, clinical significance) is crucial.
• Identifying risks and implementing interventions for diseases.
• Disease prevention and disease mitigation.

Why GEIs Are Important

• GEI research aids in understanding disease mechanisms.
• It improves disease prediction and enables better prevention strategies.
• It also influences drug efficacy, safety, public health interventions.

GEIs' Contribution to Understanding Disease

• GEIs can help researchers understand disease mechanisms.
• They analyze the combined effect of genes and environment on health outcomes.
• Focusing on the impact of genetic and environmental factors, not only genetic factors alone.

Behavioral and Systemic Consequences

• Environmental exposures affect health and illness not only at the cellular level but also via behavioral and systemic consequences.
• Toxic exposures can affect cellular functions.
• Lifestyle factors can modify phenotypes by affecting brain networks or hormone levels.
• Environmental factors encompass a diverse range of biological systems from cellular to organism level, interacting intricately with genetics.

Exposure Measurement

• Exposome Definition: Encompasses all lifetime environmental exposures (external and internal, e.g., pollution, social factors, microbiome, oxidative stress).

Measurement Techniques

• 1- Mass Spectrometry (MS): High-throughput, untargeted MS detects pollutants, food additives, and internal metabolites.
• 2- Sensors and machine learning to better understand GEIs.
• 3- Wearable devices that track pollution exposure and the body's response.
• 4- Questionnaires: Collect data on lifestyle, exposures, and social health factors; standardization issues, recall bias, cultural differences are drawbacks; to improve accuracy, questionnaires are increasingly integrated with exposure data.

Challenges with Standardizing the Exposome

• High disease risk from environmental exposures is difficult to quantify accurately.
• Measurement challenges exist due to the exposome's lack of standardized measurement methods.
• Overlapping risk estimates can occur.
• The interplay of genetics and environment makes accurately estimating GEI contributions complex.

Disease and Environmental Factors

• Diseases like cardiovascular disease, type 2 diabetes, asthma, respiratory diseases, cancer, and neurodegenerative diseases (e.g., Alzheimer's) are significantly influenced by environmental factors.
• The contribution of environmental factors and estimated heritability percentages for certain diseases are listed.

GEI Analysis Advantages

• Incorporates genetic and environmental factors affecting complex traits.
• Enhancing understanding of disease mechanisms and individual heterogeneity (differences).
• Addresses missing heritability (the portion of heritability that isn't explained by genetic factors alone).
• Established associations (e.g., air pollution—cardiovascular disease, smoking—lung cancer, etc).

GEI Analysis Advantages: Improved Prediction and Statistical Power

• GEI analyses explain more phenotypic variance than traditional genome-only analyses.
• Using the exposome framework captures additive and non-additive effects and improves the power of health phenotype analyses.
• Enhanced polygenic scores (PGS) predictive power across diverse populations.

Examining GEI Analysis Compared to Genome Analyses

• A major benefit of GEI analysis is that it includes environmental factors that impact health.

Established Associations Identified by GEI Studies

• Air pollution and cardiovascular disease are an established association identified by GEI studies

How to Identify GEIs

• Family studies help differentiate between genetic and environmental risks; they highlight population heterogeneity.
• Genetic markers are crucial for assessing ancestry and improving study design, which helps account for population stratification and reduce selection bias.

Environmental Effect Identification Methods

• Enhanced detection of environmental effects in subgroups.
• Genetic effects may only be evident when stratified by exposure levels.

Candidate Genes in GEI Studies

• Selection context depends on existing knowledge.
• Classes of Environmentally Responsive Genes, such as Cytochrome P450 Enzymes (CYPs), DNA Repair Genes, Metabolic Genes, Antioxidant Genes, Heat Shock Proteins, Xenobiotic Receptors, Inflammatory Response Genes, Transporter Genes.

Epidemiology's Role in GEI Studies

• Epidemiology contributes to GEI studies by collecting standardized data on disease outcomes and exposures.

Epigenetics Overview

• Epigenetics studies non-sequence modifications to DNA and chromatin that affect gene accessibility and regulation.
• Gene-Environment Interactions (GEIs): connecting genetic makeup to environmental exposures; contribute to disease development.
• Environmental factors alter epigenetic markers, influencing cell communication and growth.
• Key modifications: DNA CpG methylation (most common and assessed method), and other types (e.g., histone modifications).
• Epigenome-Wide Association studies (EWAS) to understand GEI mechanisms, high-density BeadChips, making studies more accessible.

Easiest Epigenetic Modification in GEI Research

• DNA CpG Methylation

GEI Translation in Personalized and Preventive Health (PEH)

• By identifying interactions between genetic variations and environmental exposures (e.g., CYP2D6 & pesticides, NAT2 & smoking, etc.), personalized interventions can be developed.
• Pharmacogenomics applies genetic information to optimize drug treatment, dosages, and to prevent hypersensitivity reactions (HLA-B*57:01 & abacavir).
• Disease Prevention: Identifying gene mutations (e.g., BAP1) linked to specific risks (e.g., asbestos exposure). Personalized health strategies can be employed.

Genetic Susceptibility/Exposure Health Impact/Applications

• Examples of GEI applications include personalized air-quality alerts, managing respiratory symptoms, mitigating lead exposure, and monitoring asbestos exposure.
• These strategies enhance disease prevention and improve health outcomes for susceptible populations.
• Other considerations might include targeted surveillance and early detection strategies.

Social and Societal Considerations in GEI Research

• Environmental justice and PEH: combine individual and community environmental data and biological data to address health disparities.
• Analyzing genetic vulnerabilities of populations to pollutants, using targeted interventions to address health issues in vulnerable groups, especially low-income populations.
• Health disparities influence gene expression through exposure differences.
• Research needs to consider racism in order to identify populations at risk for lasting epigenetic changes due to previous toxic exposures and stress, in order to create interventions that benefit both current and future generations.

Return of Results in GEI Research

• Ethical considerations for returning GEI study findings to participants.
• Routine report-backs, community-guided report-backs, and supportive resources.
• Clear communication to stakeholders, participants, and communities; actionable health improvements, and data protection (privacy and re-identification).

Data Privacy in GEI Research

• Data privacy concerns regarding environmental exposure data (especially geospatial data) are identified.
• Safeguards (e.g., encryption, access controls, informed consent) to protect collected data are vital.
• Risks of re-identification of participants and potential impact on public trust.

Conclusion

• Understanding GEIs helps predict disease risks more accurately and create better treatments.
• Future research will focus on more accurate ways to measure environmental exposures and study diverse populations to improve our understanding of disease mechanisms and health outcome differences.

References

• A URL is provided.

Test your knowledge on Gene-Environment Interactions (GEIs) and their significance in research. This quiz covers various aspects such as measurement techniques, limitations of questionnaires, and the contributions of environmental factors to disease risk. Engage with questions about the exposome and the role of technology in studying GEIs.