Dataset Information

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.

ABSTRACT: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations.To assess the association of these genes with T2DM risk in a South African mixed-ancestry population.Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits.In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals.Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.

SUBMITTER: Yako YY

PROVIDER: S-EPMC4765404 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.

Yako Yandiswa Y YY Madubedube Jabulisile H JH Kengne Andre P AP Erasmus Rajiv T RT Pillay Tahir S TS Matsha Tandi E TE

African health sciences 20151201 4

<h4>Background</h4>Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations.<h4>Objectives</h4>To assess the association of these genes with T2DM risk in a South African mixed-ancestry population.<h4>Methods</h4>Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs375 ...[more]

PMID: 26958016

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Project description:Admixed populations can make an important contribution to the discovery of disease susceptibility genes if the parental populations exhibit substantial variation in susceptibility. Admixture mapping has been used successfully, but is not designed to cope with populations that have more than two or three ancestral populations. The inference of admixture proportions and local ancestry and the imputation of missing genotypes in admixed populations are crucial in both understanding variation in disease and identifying novel disease loci. These inferences make use of reference populations, and accuracy depends on the choice of ancestral populations. Using an insufficient or inaccurate ancestral panel can result in erroneously inferred ancestry and affect the detection power of GWAS and meta-analysis when using imputation. Current algorithms are inadequate for multi-way admixed populations. To address these challenges we developed PROXYANC, an approach to select the best proxy ancestral populations. From the simulation of a multi-way admixed population we demonstrate the capability and accuracy of PROXYANC and illustrate the importance of the choice of ancestry in both estimating admixture proportions and imputing missing genotypes. We applied this approach to a complex, uniquely admixed South African population. Using genome-wide SNP data from over 764 individuals, we accurately estimate the genetic contributions from the best ancestral populations: isiXhosa [Formula: see text], ‡Khomani SAN [Formula: see text], European [Formula: see text], Indian [Formula: see text], and Chinese [Formula: see text]. We also demonstrate that the ancestral allele frequency differences correlate with increased linkage disequilibrium in the South African population, which originates from admixture events rather than population bottlenecks.The collective term for people of mixed ancestry in southern Africa is "Coloured," and this is officially recognized in South Africa as a census term, and for self-classification. Whilst we acknowledge that some cultures may use this term in a derogatory manner, these connotations are not present in South Africa, and are certainly not intended here.

Dataset Information

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.

Publications

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa.

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