Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore

Tan, Jonathan T.; Ng, Daniel P.K.; Nurbaya, Siti; Ye, Sandra; Lim, Xiu-Li; Leong, Helen; Seet, Lin Tze; Siew, Wei Fong; Kon, Winston; Wong, Tien Yin; Saw, Seang Mei; Aung, Tin; Chia, Kee Seng; Lee, Jeannette; Chew, Suok Kai; Seielstad, Mark; Tai, E. Shyong

doi:10.1210/jc.2009-0688

Cited by 74 publications

(30 citation statements)

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“…Meanwhile, both rs11187007 and rs1111875 were identified to be associated with type 2 diabetes risk after further adjustment for age, gender and BMI (for both variants: OR¼1.15, 95% CI 1.04-1.28, P¼0.009 in an additive model; Table 1). In addition, meta-analysis of six populations, total individuals of 15 467 Chinese (7207 cases and 8260 controls) 3,5,6,28 confirmed the association of the HHEX rs1111875 with type 2 diabetes (OR¼1.15, 95% CI 1.10-1.21, P¼1.93Â10 À8 ) ( Table 3).…”

Section: Resultsmentioning

confidence: 80%

“…In the past two decades, a total of 18 loci have been confirmed as type 2 diabetes risk loci with modest effect sizes in populations of European descent. 1,2 Although most of these same loci have been confirmed to be associated with type 2 diabetes in Chinese, [3][4][5][6] differences in allele frequency, genetic background, lifestyle and environmental exposures may lead to inconsistent results or different effect size of some genetic variants on type 2 diabetes risk between Chinese and European (for example, TCF7L2, HHEX-IDE, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5). 3,6 The association between the five loci (JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, VEGFA and ADAMTS9) and type 2 diabetes were first identified by Zeggini et al 7 with meta-analysis of three genome-wide association studies.…”

Section: Introductionmentioning

confidence: 99%

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Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

et al. 2010

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Several genetic loci (JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, ADAMTS9, VEGFA and HHEX-IDE) were identified to be significantly related to the risk of type 2 diabetes and quantitative metabolic traits in European populations. Here, we aimed to evaluate the impacts of these novel loci on type 2 diabetes risk in a population-based case-control study of Han Chinese (1912 cases and 2041 controls). We genotyped 13 single-nucleotide polymorphisms (SNPs) in/near these genes and examined the differences in allele/genotype frequency between cases and controls. We found that both IDE rs11187007 and HHEX rs1111875 were associated with type 2 diabetes risk (for both variants: odds ratio (OR)¼1.15, 95% confidence interval (CI) 1.04-1.28, P¼0.009). In a meta-analysis where we pooled our data with the three previous studies conducted in East Asians, we found that the variants of JAZF1 rs864745 (1.09 (1.03-1.16); P¼3.49Â10 À3 ) and TSPAN8/LGR5 rs7961581 (1.11 (1.05-1.17); P¼1.89Â10 À4 ) were significantly associated with type 2 diabetes risk. In addition, the meta-analysis (7207 cases and 8260 controls) also showed that HHEX rs1111875 did have effects on type 2 diabetes in Chinese population (OR¼1.15(1.10-1.21); P¼1.93Â10 À8 ). This large population-based study and meta-analysis further confirmed the modest effects of the JAZF1, TSPAN8/LGR5 and HHEX-IDE loci on type 2 diabetes in Chinese and other East Asians.

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Section: Resultsmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

et al. 2010

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“…Recent studies have shown that multiple type 2 diabetes susceptibility genes reported in European populations have either failed to show association in people of African ancestry (Lewis et al 2008) or showed modest contribution to variation in glucose homeostasis (Yang et al 2010). By comparison, single nucleotide polymorphisms at type 2 diabetes susceptibility loci identified through GWAS in populations of European ancestry have been shown to have similar effects in Asian (Tan et al 2010) and Mexican American (Yang et al 2010) populations suggesting that the genetic risk factors may not be identical in different ethnic and racial groups.…”

Section: Discussionmentioning

confidence: 99%

Reasons for participating and genetic information needs among racially and ethnically diverse biobank participants: a focus group study

et al. 2011

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In order for DNA biobanks to be a valuable reservoir of genetic information, large numbers of participants from all racial and ethnic backgrounds need to be recruited. This study explored reasons for participating in a new biobank among primarily Hispanic and African American individuals, as well as their general attitudes towards genetic research, and their views on obtaining genetic tests. Focus groups were conducted with Mount Sinai Biobank participants recruited from predominantly lower income, minority communities. The topic guide included questions on The Mount Sinai Biobank, genetic research, and genetic testing. All focus groups were audio recorded, transcribed, and analyzed using thematic analysis. The six focus groups comprised 43 participants: 39 females and four males, aged 27-76 years, with a median household income category of $20,000-$39,999. Twenty-one participants were Hispanic, 20 African American, one Asian, and one White. Participants' reasons for participating in the biobank included altruism, personal and family benefit, and general curiosity. Although there was evidence of conflation between genetic research and genetic testing, most participants held positive views of genetic research and expressed interest in receiving personal genetic test results. Participants wanted to learn more about genetic research and suggested various venues such as health fairs for disseminating information. Participation in biobanks by racial and ethnic minorities is apparently driven by altruism, and desire for personal or collective health benefits. genetics and genetic research, and made useful suggestions regarding information dissemination mechanisms.

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“…Very recently, two GWAS studies on Chinese Han and European populations confirmed KCNQ1 as a T2DM susceptibility gene (Tsai et al, 2010;Voight et al, 2010). The association of T2DM with KCNQ1 variants was replicated in studies on Chinese (Hu et al, 2009;Liu et al, 2009;Qi et al, 2009), Singaporean (Tan et al, 2009(Tan et al, , 2010, Indian (Been et al, 2011), and some Euro-Caucasian subjects (Unoki et al, 2008;Holmkvist et al, 2009;Jonsson et al, 2009).…”

Section: Introductionmentioning

confidence: 90%

Relationship between the polymorphisms in KCNQ1 and type 2 diabetes in Chinese Kazakh population

Cui¹,

Xy²,

Ly³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Recently genome-wide association studies on East Asian populations reported an association between diabetes and several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium block in intron 15 of KCNQ1. However, the association between KCNQ1 variants and type 2 diabetes mellitus (T2DM) in Chinese Kazakh populations is unknown. We investigated the relationship between rs2237892 and rs2237895 SNPs in KCNQ1 and susceptibility to and clinical characteristics of T2DM in 100 Chinese Kazakh T2DM subjects and 100 healthy subjects. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and the main anthropometric and biochemical parameters of individuals were assessed in the genotype groups (rs2237892: CC, CT, or TT, and rs2237895: AA, AC, or CC). Genotype distribution and allele frequencies of these two SNPs were not significantly different between T2DM and control groups (P > 0.05). The frequencies of CT and TT genotypes and T allele for the rs2237892 SNP in females with T2DM were significantly higher than that in the control group (genotype: P = 0.016, allele: P = 0.004). However, there were no significant differences among individuals with different genotypes with respect to the rs2237895 SNP (P > 0.05). The main anthropometric and biochemical parameters did not correlate with the rs2237892 or rs2237895 SNPs in the T2DM group (P > 0.05). Thus, the T allele-containing genotypes of the rs2237892 SNP in KCNQ1 may increase the susceptibility to T2DM in female Chinese Kazakh individuals, whereas the rs2237895 SNP may not be associated with T2DM in the Chinese Kazakh population.

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Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore

Cited by 74 publications

References 0 publications

Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

Reasons for participating and genetic information needs among racially and ethnically diverse biobank participants: a focus group study

Relationship between the polymorphisms in KCNQ1 and type 2 diabetes in Chinese Kazakh population

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