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| 12. |
- Kooner, Jaspal S, et al.
(författare)
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Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:10
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.
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| 13. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 14. |
- Tan, Kristin H. X., et al.
(författare)
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Diabetes mellitus prevalence is increasing in South Asians but is stable in Chinese living in Singapore and Mauritius
- 2017
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Ingår i: Journal of Diabetes. - : John Wiley & Sons. - 1753-0393 .- 1753-0407. ; 9:9, s. 855-864
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asia is experiencing a type 2 diabetes epidemic but prevalence differs by ethnicity and level of socio-economic development. Singapore and Mauritius have implemented comprehensive campaigns to address this public health problem. We compared diabetes and obesity prevalence trends among Chinese and South Asians living in Singapore and Mauritius to determine the contribution of ethnicity and economic development to diabetes.METHODS: Age-specific data from serial national population-based surveys in Singapore and Mauritius between 1987 and 2010 were used to estimate age-standardised diabetes and obesity prevalence. Modified Breslow-Cox Proportional hazard models were used to obtain rate ratios for diabetes risk factors.RESULTS: In Singapore, the age-standardised prevalence of diabetes remained stable for Chinese (men 14% in 1992 and 13% in 2010; women 12% in 1992 and 10% in 2010); however, increases were observed for South Asians (men 20% in 1992 and 26% in 2010; women 18% in 1992 and 20% in 2010). There were similar patterns in Mauritius. In both countries, obesity prevalence trends were stable for Chinese women, but increased for Chinese men and South Asians. Associations between obesity and diabetes were stronger in Chinese than South Asians irrespective of country.CONCLUSIONS: Despite different socio-economic settings in Singapore and Mauritius, we observed rising diabetes prevalence among South Asians but stable prevalence in Chinese in both countries. This provides further evidence that ethnicity contributes to the development of diabetes, and that there should be an increased emphasis on future prevention strategies targeting South Asian populations in these countries.
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