Decanalization and the origin of complex disease

Area of Science:

• Genetics
• Environmental Health
• Epidemiology

Background:

• Complex genetic diseases are a leading cause of global mortality.
• These diseases result from intricate interactions between genetic and environmental factors.
• Nonlinear influences of multiple genetic pathways on liability suggest 'decanalization' contributes to disease epidemics.

Purpose of the Study:

• To explore the role of genetic and environmental interactions in complex diseases.
• To investigate the concept of 'decanalization' in the context of common genetic diseases.
• To understand how recent genomic and environmental changes may uncover cryptic genetic variation.

Main Methods:

• The study is primarily theoretical, synthesizing existing research on genetics, environment, and disease.
• It involves analyzing the implications of nonlinear genetic interactions and rapid environmental shifts.
• Focuses on the concept of human genome evolution and its interaction with environmental perturbations.

Main Results:

• Complex genetic diseases stem from gene-environment interplay, a major cause of death worldwide.
• The nonlinear combination of multiple genetic pathways influencing liability factors points to 'decanalization' as a driver of common genetic disease epidemics.
• Rapid human genome evolution and recent environmental changes may expose previously hidden genetic variations, increasing disease susceptibility.

Conclusions:

• Understanding gene-environment interactions is crucial for addressing complex genetic diseases.
• Decanalization offers a framework for comprehending the epidemic nature of common genetic disorders.
• Cryptic genetic variation, potentially uncovered by recent evolutionary and environmental pressures, represents a significant factor in disease susceptibility.