Campbell, DD;
Parra, MV;
Duque, C;
Gallego, N;
Franco, L;
Tandon, A;
Hünemeier, T;
... Ruiz-Linares, A; + view all
(2012)
Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population.
PLOS One
, 7
(4)
, Article e33570. 10.1371/journal.pone.0033570.
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Abstract
The "thrifty genotype" hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ~95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05).
| Type: | Article |
|---|---|
| Title: | Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0033570 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0033570 |
| Language: | English |
| Additional information: | © 2012 Campbell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The authors are very grateful to the volunteers that contributed samples for this project. AP was supported by a Ruth Kirschstein National Research Service Award from the National Institutes of Health (NIH). This work was partially funded by discretionary funding from Harvard Medical School (to DR), NIH grants NS043538 (to AR-L) and DK073818 (to DR), Colciencias grants 1115-04-16451 and 1115-04-012986 (to GB and AV), and a Universidad de Antioquía grant [CODI/sostenibilidad 9889-E01321] (to GB and AV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Alleles, Body Mass Index, Case-Control Studies, Colombia, Diabetes Mellitus, Type 2, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Indians, South American, Lod Score, Polymorphism, Single Nucleotide, Social Class |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1369333 |
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