Individual Estimates of European Genetic Admixture Associated with Lower Body-Mass Index, Plasma Glucose, and Prevalence of Type 2 Diabetes in Pima Indians
Open accessAbstract
Individual genetic admixture estimates (IA) from European Americans (EAs) were computed in 7,996 members of the Gila River Indian Community (Arizona). Parental populations for the analysis were European Americans and full-heritage Pima Indians. A logistic regression was performed on 7,796 persons, to assess association of IA with type 2 diabetes. The odds ratio, comparing diabetes risk in full-heritage EAs with full-heritage Pima Indians, was 0.329 (95% confidence interval [CI] 0.225-0.482). Proportional-hazards analysis was performed on 5,482 persons who were nondiabetic at their first examination and 1,215 subjects who developed diabetes during the study. The hazard risk ratio for IA was 0.455 (95% CI 0.301-0.688). Nondiabetic persons had significantly more European IA. In nondiabetic Pimans, multivariate linear regressions of quantitative predictors of type 2 diabetes mellitus, including fasting plasma glucose, 2-h post-load plasma glucose, and body-mass index, showed significant inverse relations with IA when controlled for sex and age. These results illustrate the ongoing evolution of populations by the mechanism of gene flow and its effect on disease risk in the groups with admixture. When the two parental populations differ in disease prevalence, higher or lower risk is associated with admixture, depending on the origin of the admixed alleles and the relative magnitude of the disease prevalence in the parental populations. These data also illustrate the strong genetic components in type 2 diabetes and are consistent with one susceptibility locus common to obesity and diabetes.
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Admixture studies generally find that admixture relates to the trait under investigation above and beyond covariates.
“These studies generally find that admixture relates to the trait under investigation above and beyond covariates.”
From Global Ancestry and Cognitive Ability (2019) · cites this paper as [38]
The Results report that genetic admixture was associated with glucose and BMI among nondiabetic Pima Indians in models adjusted for age and sex; they found no significant association for those traits in the diabetic group. The paper supports this study as an example, but its findings do not establish that admixture studies generally find associations beyond covariates. (LLM, conf=0.84)
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“Marked ethnic disparities are seen in rates of obesity, and concomitantly in rates of diabetes, and a few studies have indicated that people with part ancestry in high risk groups have an intermediate risk for obesity (Albright et al., 2007; Tang et al., 2006; Williams et al., 2000).”
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Global Ancestry and Cognitive Ability
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Genetic Basis of Type 2 Diabetes Mellitus
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“[1] The largest ture,[19] is strongly suggestive of a genetic component to the increases in type 2 diabetes are expected to occur in developed and disease.”
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“In contrast, Tang et al. (2006) found a statistically significant positive relationship between the degree of European admixture and BMI in a sample of Mexican Americans, a result that is potentially inconsistent with the findings of Williams et al. (2000) and Sweeney et al. (2007).”
BackgroundResultGenetics of Type 2 Diabetes: the Power of Isolated Populations
Andersen, M. K., Pedersen, C. T., Moltke, I., Hansen, T. F., Albrechtsen, A., & Grarup, N. (2016) · Current Diabetes Reports · doi:10.1007/s11892-016-0757-z · Cited by 27 · see citing works
A new era in finding Type 2 diabetes genes—the unusual suspects
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“This variation may be due to environmental, epigenetic, or genetic variation (Williams et al., 2000; Fernández et al., 2003; Tang et al., 2006; Cheng et al., 2010).”
BackgroundPollard, T. M. (2001) · Cambridge University Press eBooks · doi:10.1017/cbo9780511841118 · Cited by 25 · see citing works
The Genetics of Type 2 Diabetes
Lindgren, C. M., & Hirschhorn, J. N. (2001) · The Endocrinologist · doi:10.1097/00019616-200105000-00004 · Cited by 21 · see citing works
Exceeding Hrdlička's aims: 100 Years of genetics in anthropology
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“…there is a unique genetic component to obesity in admixed populations such as Native Americans, African Americans, and Mexican Americans (Angeli et al., 2011; Ehlers and Wilhelmsen, 2007; Klimentidis et al., 2009b; Ma et al., 2010; Nassir et al., 2012; Peterson et al., 2011; Williams et al., 2000).”
BackgroundResultInfluentialWilliams, R. C., Knowler, W. C., Shuldiner, A. R., Gosalia, N., Hout, C. V. V., Hanson, R. L., Bogardus, C., & Baier, L. J. (2019) · Human Immunology · doi:10.1016/j.humimm.2019.10.002 · Cited by 17 · see citing works
Self-citationFrom the Old World to the New World: an ecologic study of population susceptibility to HIV infection
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Genotypes, obesity and type 2 diabetes – can genetic information motivate weight loss? A review
Gable, D. R., Sanderson, S. C., & Humphries, S. E. (2007) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2007.070 · Cited by 16 · see citing works
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“Se ha demostrado que la prevalencia de diabetes mellitus tipo 2 está muy correlacionada con la ascendencia amerindia (15), que en poblaciones hispánicas de Estados Unidos las personas con ascendencia africana tiene mayor prevalencia de diabetes mellitus tipo 2 que las que poseen ascendencia europea (16) y que el riesg…”
BackgroundPenicillin Production from Transformed Protoplast of Penicillium chrysogenum by Fermentation
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“type 2 diabetes mellitus in the Pima Indian population [8]; differences in relative European ancestry proportions correlate with higher susceptibility in Puerto Ricans to asthma as compared with Mexicans [9]; and the increased risk of cardiovascular disease and hypertension in Puerto Ricans from Boston with greater Af…”
BackgroundGenetic and environmental adaptation in high altitude natives
Brutsaert, T. D. (2001) · Advances in experimental medicine and biology · doi:10.1007/978-1-4757-3401-0_10 · Cited by 13 · see citing works
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“Only 9.5% of the North American Amerindian samples surveyed by Post et al. (1968) showed no European admixture, while 65% of the samples exhibited 5% or higher admixture (see also Szathmary and Auger, 1983; Crawford, 1998; Williams et al., 2000 ).”
BackgroundInfluentialAdmixture mapping as a gene discovery approach for complex human traits and diseases
Nievergelt, C. M., & Schork, N. J. (2005) · Current Hypertension Reports · doi:10.1007/s11906-005-0052-x · Cited by 12 · see citing works
“For example, increased susceptibility to abnormal levels of insulin secretion [32], and to resting metabolic rate and obesity [31], has been associated with higher individual African ancestry proportions, whereas a negative association between European admixture and prevalence for type 2 diabetes and obesity in Pima I…”
BackgroundAdmixture, Genetics and Complex Diseases in Latin Americans and US Hispanics
Soares‐Souza, G. B., Borda, V., Kehdy, F. S. G., & Tarazona‐Santos, E. (2018) · Current Genetic Medicine Reports · doi:10.1007/s40142-018-0151-z · Cited by 13 · see citing works
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“We did not observe a significant association between Native American ancestry and adiposity, although Native Americans as a group are reported to have greater obesity risk compared to non-Hispanic whites [39].”
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“Differences in QTL effects between ancestry groups were reported in human populations (Williams et al. 2000) with variable amplitude, up to opposite sign effects (Deng 2001).”
BackgroundA population genetics model of linkage disequilibrium in admixed populations
Tao, S., Zhang, R., Chu, J., Liu, X., Du, L., Qi, Q., & Luo, Z. (2001) · Chinese Science Bulletin · doi:10.1007/bf03187164 · Cited by 7 · see citing works
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“While much work remains to be done, genetics may explain, for example, why LatAm has a comparatively high prevalence of type II diabetes (risk associated with Native American ancestry) [4].”
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Linear and partially linear models of behavioral trait variation using admixture regressionPreprint
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“A similar finding has also been reported for the Pima of Arizona (Williams et al. 2000).”
ResultGenetic determinants of cardiovascular disease in Hispanics
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“Differences in genetic makeup may not confer an identical risk of disease in all populations, and research has demonstrated associations of genetic ancestral background with outcomes related to CVD, such as diabetes [ 46 ] and obesity-related concerns [44,47] in Hispanics.”
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A life course approach to diabetes
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An evolutionary history of human disease
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- Authors
- Williams, R. C., Long, J. C., Hanson, R. L., Sievers, M. L., & Knowler, W. C.
- Affiliations
- Arizona State University (US)
- National Institute on Alcohol Abuse and Alcoholism (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Corresponding author
- Williams, Robert C.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 66
- Issue
- 2
- Pages
- 527-538
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1288106
- OpenAlex
- W2074697500
- Cited by
- 112
- References
- 39
- Citations by year
- 2023: 2 · 2021: 2 · 2020: 1 · 2019: 6 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 1 · 2012: 3
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Race, Genetics, and Society
- Keywords
- type 2 diabetes, Pima Indians, Gila River Indian Community, body mass index, fasting blood glucose, gene flow, disease susceptibility, obesity, diabetes risk, admixture mapping
- MeSH terms
- Age Factors, Alleles, Blood Glucose, Child, Diabetes Mellitus, Type 2, Europe, Fasting, Female, Gene Frequency, Humans, Indians, North American, Male, Obesity, Sex Factors, Genetic Variation, Body Mass Index, Prevalence, Logistic Models, Proportional Hazards Models, Odds Ratio, Genetic Predisposition to Disease
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