ReviewEvolution, medicine, and public health2024
Integrating the Thrifty Genotype and Evolutionary Mismatch Hypotheses to understand variation in cardiometabolic disease risk.
Review in Evolution, medicine, and public health, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Selective advantages, selective mismatches, chronic inflammation, obesity, and type 2 diabetes: a new hypothesis to explain the effects of natural selection on genetic variation at the ectodysplasin A receptor locus.BMJ open diabetes research & care · 2026Review
- Selection-guided discovery in South Asians implicates the MAPT locus in insulin resistance.medRxiv : the preprint server for health sciences · 2026Article
- Genome-Based Mexican Diet Bioactives Target Molecular Pathways in HBV, HCV, and MASLD: A Bioinformatic Approach for Liver Disease Prevention.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
More than 60 years ago, James Neel proposed the Thrifty Genotype Hypothesis to explain the widespread prevalence of type 2 diabetes in Western, industrial contexts. This hypothesis posits that variants linked to conservative energy usage and increased fat deposition would have been favored throughout human evolution due to the advantages they could provide during periods of resource limitation. However, in industrial environments, these variants instead produce an increased risk of obesity, metabolic syndrome, type 2 diabetes, and related health issues. This hypothesis has been popular and impactful, with thousands of citations, many ongoing debates, and several spin-off theories in biomedicine, evolutionary biology, and anthropology. However, despite great attention, the applicability and utility of the Thrifty Genotype Hypothesis (TGH) to modern human health remains, in our opinion, unresolved. To move research in this area forward, we first discuss the original formulation of the TGH and its critiques. Second, we trace the TGH to updated hypotheses that are currently at the forefront of the evolutionary medicine literature-namely, the Evolutionary Mismatch Hypothesis. Third, we lay out empirical predictions for updated hypotheses and evaluate them against the current literature. Finally, we discuss study designs that could be fruitful for filling current knowledge gaps; here, we focus on partnerships with subsistence-level groups undergoing lifestyle transitions, and we present data from an ongoing study with the Orang Asli of Malaysia to illustrate this point. Overall, we hope this synthesis will guide new empirical research aimed at understanding how the human evolutionary past interacts with our modern environments to influence cardiometabolic health.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.