Applying an evolutionary mismatch framework to understand disease susceptibility
Document Type
Article
Publication Date
9-1-2023
Abstract
Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of ``lifestyle'' diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be ``mismatched'' and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit ``genotype by environment'' (GxE) interactions, with different health effects in ``ancestral'' versus ``modern'' environments. To identify such loci, we advocate for combining genomic tools with partnerships with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the ``matched'' to ``mismatched'' spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures. Humans evolved in environments that radically differ from those we currently experience; thus, traits that were once advantageous may now be ``mismatched'' and disease-causing. In this Essay, the authors advocate for combining genomic tools with partnerships with subsistence-level groups experiencing rapid lifestyle change to identify genetic loci associated with disease risk.
Keywords
Gene-Environment interaction, Body mass index, Epidemiology
Divisions
fac_med
Funders
Canadian Institute for Advanced Research (CIFAR),Searle Scholars Program, and National Institutes of Health NIGMS - R35-GM147267,United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIEHS R01ES029929
Publication Title
PLOS Biology
Volume
21
Issue
9
Publisher
Public Library Science
Publisher Location
1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA