Canalization and Robustness in Human Genetics and Disease

Area of Science:

• Evolutionary biology
• Genetics
• Disease ecology

Background:

• Canalization is the evolutionary process minimizing population deviation from optimal traits and disease.
• Decanalization, the reverse process, may explain rising disease prevalence amid rapid environmental, cultural, or genetic shifts.
• Distinguishing population canalization from individual robustness is crucial for understanding disease dynamics.

Purpose of the Study:

• To review the concepts of canalization and decanalization in evolutionary and disease contexts.
• To evaluate existing evidence for decanalization across human traits and diseases.
• To explore the potential of new genetic risk assessment tools for studying canalization's role in disease prevention.

Main Methods:

• Literature review defining canalization and robustness.
• Examination of genetic evidence for genotype-by-environment interactions related to three continuous traits and six disease domains.
• Consideration of rare and common genetic variants' contributions to congenital and adult-onset diseases using a novel 'kerplunk' model.

Main Results:

• Current genetic evidence for genotype-by-environment interactions is insufficient to strongly infer decanalization.
• Genome-wide polygenic risk scores offer a new empirical approach to assess canalization's impact on disease.
• The 'kerplunk' model provides a framework for analyzing genetic variant contributions to disease.

Conclusions:

• Decanalization is a plausible contributor to increased disease prevalence during periods of rapid change.
• Advances in polygenic risk assessment enable empirical testing of canalization's role in disease prevention.
• Further research is needed to fully elucidate the genetic architecture of canalization and its implications for public health.