The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants?
Open accessAbstract
AIMS/HYPOTHESIS: According to the thrifty genotype hypothesis, the high prevalence of type 2 diabetes and obesity is a consequence of genetic variants that have undergone positive selection during historical periods of erratic food supply. The recent expansion in the number of validated type 2 diabetes- and obesity-susceptibility loci, coupled with access to empirical data, enables us to look for evidence in support (or otherwise) of the thrifty genotype hypothesis using proven loci. METHODS: We employed a range of tests to obtain complementary views of the evidence for selection: we determined whether the risk allele at associated 'index' single-nucleotide polymorphisms is derived or ancestral, calculated the integrated haplotype score (iHS) and assessed the population differentiation statistic fixation index (F (ST)) for 17 type 2 diabetes and 13 obesity loci. RESULTS: We found no evidence for significant differences for the derived/ancestral allele test. None of the studied loci showed strong evidence for selection based on the iHS score. We find a high F (ST) for rs7901695 at TCF7L2, the largest type 2 diabetes effect size found to date. CONCLUSIONS/INTERPRETATION: Our results provide some evidence for selection at specific loci, but there are no consistent patterns of selection that provide conclusive confirmation of the thrifty genotype hypothesis. Discovery of more signals and more causal variants for type 2 diabetes and obesity is likely to allow more detailed examination of these issues.
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“Based on an analysis of 17 type 2 diabetes loci and 13 obesity loci, Southam et al. (48) found no clear evidence for overrepresentation of derived alleles (vs. ancestral alleles) for the obesity or diabetes loci or greater concentration of these loci in a particular ethnic group.”
From Globalization of Diabetes (2011) · cites this paper as [48]
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Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
Faith, M. S., Carnell, S., & Kral, T. V. E. (2013) · Human Heredity · doi:10.1159/000353879 · Cited by 7,633
Lippa, N. C., & Sanderson, S. C. (2013) · Human Heredity · doi:10.1159/000353712 · Cited by 6,095
Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R. B., Elliott, K. S., Lango, H., Rayner, N. W., et al. (2007) · Science · doi:10.1126/science.1141634 · Cited by 4,531
A second generation human haplotype map of over 3.1 million SNPs
The International HapMap Consortium (2007) · Nature · doi:10.1038/nature06258 · Cited by 4,438
Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"?
Neel, J. V. (1962) · Europe PMC (PubMed Central) · Cited by 3,172
A Map of Recent Positive Selection in the Human Genome
Voight, B. F., Kudaravalli, S., Wen, X., & Pritchard, J. K. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040072 · Cited by 2,925
Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"?
(1962) · PubMed Central · Cited by 2,182
the GIANT Consortium (2009) · Nature Genetics · doi:10.1038/ng.287 · Cited by 1,720
Thorleifsson, G., Walters, G. B., Gudbjartsson, D. F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I., et al. (2009) · Nature Genetics · doi:10.1038/ng.274 · Cited by 1,375
Common variants near MC4R are associated with fat mass, weight and risk of obesity
The Prostate, L., Loos, R. J. F., KORA, Study, N. H., Initiative, D. G., Study, T. S., The Wellcome Trust Case Control Consortium, FUSION, Lindgren, C. M., Li, S., et al. (2008) · Nature Genetics · doi:10.1038/ng.140 · Cited by 1,325
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Qasim, A., Turcotte, M., de Souza, R. J., Samaan, M. C., Champredon, D., Dushoff, J., Speakman, J. R., & Meyre, D. (2018) · Obesity Reviews · doi:10.1111/obr.12625 · Cited by 241
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Metadata
- Authors
- Southam, L., Soranzo, N., Montgomery, S. B., Frayling, T. M., McCarthy, M. I., Barroso, I., & Zeggini, E.
- Affiliations
- Centre for Human Genetics (GB)
- St Thomas' Hospital (GB)
- Wellcome Sanger Institute (GB)
- University of Exeter (GB)
- Corresponding author
- Zeggini, E.
- Venue
- Diabetologia
- Published
- 2009-06-13
- Volume
- 52
- Issue
- 9
- Pages
- 1846-1851
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC2723682
- OpenAlex
- W2071881237
- Cited by
- 103
- References
- 15
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 8 · 2022: 2 · 2021: 6 · 2020: 2 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 12 · 2013: 8 · 2012: 13
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Diabetologia (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (WT077016/Z/05/Z, 088885, 077016, WT088885/Z/09/Z, 079557)
- National Institute for Health and Care Research
- Medical Research Council (G0601261)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- thrifty genotype hypothesis, type 2 diabetes, obesity, genetic susceptibility loci, positive selection, integrated haplotype score, fixation index, TCF7L2
- MeSH terms
- Diabetes Mellitus, Type 2, Food Supply, Gene Frequency, Genotype, Humans, Models, Genetic, Obesity, Risk Factors, Selection, Genetic, Prevalence, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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