Lea, Amanda J. and Clark, Andrew G. and Dahl, Andrew W. and Devinsky, Orrin and Garcia, Angela R. and Golden, Christopher D. and Kamau, Joseph and Kraft, Thomas S. and Lim, Yvonne A. L. and Martins, Dino J. and Mogoi, Donald and Pajukanta, Paeivi and Perry, George H. and Pontzer, Herman and Trumble, Benjamin C. and Urlacher, Samuel S. and Venkataraman, Vivek V. and Wallace, Ian J. and Gurven, Michael and Lieberman, Daniel E. and Ayroles, Julien F. (2023) Applying an evolutionary mismatch framework to understand disease susceptibility. PLOS Biology, 21 (9). ISSN 1544-9173, DOI https://doi.org/10.1371/journal.pbio.3002311.
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| 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 |
| Uncontrolled Keywords: | Gene-Environment interaction; Body mass index; Epidemiology |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 11 Oct 2025 13:16 |
| Last Modified: | 11 Oct 2025 13:16 |
| URI: | http://eprints.um.edu.my/id/eprint/48153 |
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