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Applying an evolutionary mismatch framework to understand disease susceptibility.

Amanda J Lea1, Andrew G Clark2, Andrew W Dahl3

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The evolutionary mismatch hypothesis explains rising noncommunicable diseases (NCDs) like obesity and diabetes. Studying genetic susceptibility in populations undergoing rapid lifestyle change can identify disease-causing gene-environment interactions.

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Area of Science:

  • Evolutionary biology
  • Human genetics
  • Public health

Background:

  • Noncommunicable diseases (NCDs) are increasing globally, including obesity, cardiovascular disease, and type 2 diabetes.
  • These conditions were historically rare but are now prevalent, suggesting environmental and genetic influences.
  • The evolutionary mismatch hypothesis proposes that human traits evolved in ancestral environments may cause disease in modern settings.

Purpose of the Study:

  • To investigate the evolutionary mismatch hypothesis by examining genotype by environment (GxE) interactions.
  • To identify genetic loci that contribute to NCDs due to differing health effects in ancestral versus modern environments.
  • To leverage genomic tools and study populations experiencing rapid lifestyle transitions.

Main Methods:

  • Advocating for the integration of genomic tools with research on subsistence-level populations undergoing rapid lifestyle change.
  • Comparing individuals at opposite ends of the 'matched' to 'mismatched' spectrum within these populations.
  • Analyzing genotype by environment (GxE) interactions at specific genetic loci.

Main Results:

  • The study proposes a novel methodology for identifying genetic loci associated with NCDs.
  • It highlights the potential for GxE interactions to explain disease prevalence in changing environments.
  • The research framework allows for the examination of health disparities across diverse ancestries.

Conclusions:

  • Understanding evolutionary mismatches is crucial for addressing the global NCD epidemic.
  • Genomic studies in rapidly transitioning populations offer unique insights into disease etiology.
  • This approach can refine our understanding of environmental and genetic risk factors for NCDs across diverse populations.