Gene-environment interactions in human disease: nuisance or opportunity?

Area of Science:

• Environmental health
• Human genetics
• Disease epidemiology

Background:

• Epidemiologic studies identify environmental risk factors for complex diseases.
• The role of specific genotypes in modulating individual responses to environmental risks remains largely unknown.
• Gene-environment interactions may explain a significant portion of 'missing heritability' in genome-wide association studies.

Purpose of the Study:

• To review the challenges and approaches in studying gene-environment interactions.
• To use asthma as a model to explore candidate gene-environment interactions.
• To propose future research directions for identifying gene-environment interactions.

Main Methods:

• Literature review focusing on asthma as a model disease.
• Discussion of methodological challenges in genome-wide approaches for gene-environment interaction identification.
• Consideration of animal models for studying gene-environment interactions.

Main Results:

• Numerous candidate gene-environment interactions for asthma risk are reported in the literature.
• Genome-wide identification of gene-environment interactions presents significant methodological hurdles.
• Elucidating the molecular mechanisms underlying these interactions is complex.

Conclusions:

• Studying gene-environment interactions is essential for understanding complex human diseases.
• Current genome-wide approaches face challenges in detecting these interactions.
• Animal models may offer insights but might not fully represent human disease genetics.
• Future research needs innovative strategies to uncover gene-environment interactions.