scholarly journals Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Han Chinese Population: A Replication Study and Meta-Analysis

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95045 ◽  
Author(s):  
Yi-Cheng Chang ◽  
Pi-Hua Liu ◽  
Yu-Hsiang Yu ◽  
Shan-Shan Kuo ◽  
Tien-Jyun Chang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chinese Population ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Han Chinese Population ◽  
Risk Variants ◽  
Genome Wide

Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes

2021 ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Masatoshi Matsunami ◽  
Momoko Horikoshi ◽  
Minoru Iwata ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Japanese Patients ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Stage 1

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

scholarly journals Identification of type 2 diabetes loci in 433,540 East Asian individuals

2019 ◽  
Author(s):  
Cassandra N Spracklen ◽  
Momoko Horikoshi ◽  
Young Jin Kim ◽  
Kuang Lin ◽  
Fiona Bragg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Studies ◽  
Meta Analysis ◽  
East Asian ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
European Populations

SUMMARYMeta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.Type 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic β cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.

scholarly journals Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

2011 ◽  
Vol 44 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Yoon Shin Cho ◽  
◽  
Chien-Hsiun Chen ◽  
Cheng Hu ◽  
Jirong Long ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
East Asians ◽  
Genome Wide

scholarly journals Structural basis of ethnic-specific variants of PAX4 associated with type 2 diabetes

2020 ◽  
Author(s):  
Jun Hosoe ◽  
Ken Suzuki ◽  
Takashi Kato ◽  
Yukinori Okada ◽  
Momoko Horikoshi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structural Analysis ◽  
Japanese Population ◽  
Association Studies ◽  
Genome Wide Association ◽  
Structural Basis ◽  
Genome Wide Association Studies ◽  
Risk Variants ◽  
Genome Wide

AbstractRecently, we conducted genome-wide association studies of type 2 diabetes (T2D) in a Japanese population, which identified 20 novel T2D loci that were not associated with T2D in Europeans. Moreover, nine novel missense risk variants, such as those of PAX4, were not rare in the Japanese population, but rare in Europeans. We report in silico structural analysis of ethnic-specific variants of PAX4, which suggests the pathogenic effect of these variants.

scholarly journals Genome-Wide Association Studies-derived susceptibility loci in Type 2 Diabetes: confirmation in a Chinese population

2012 ◽  
Vol 35 (5) ◽  
pp. 327 ◽  
Author(s):  
Shuangyan Lu ◽  
Yan Xie ◽  
Kun Lin ◽  
Siwei Li ◽  
Yidan Zhou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chinese Population ◽  
Association Studies ◽  
Genome Wide Association ◽  
Diabetic Patients ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Type 2 Diabetic Patients ◽  
Genome Wide

Purpose: Several novel genetic variants for type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWAS). A case-controll study was performed to investigate the association of five new European or South Asian GWAS-derived susceptibility loci with T2DM in a Chinese population. Methods: Five single nucleotide polymorphisms (SNPs) were genotyped: rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, and rs231362 near KCNQ1, by high-resolution melting (HRM) of small amplicons. The association between T2DM and related quantitative traits in a total of 900 Chinese individuals, including 498 type 2 diabetic patients and 402 ethnically matched control subjects, were examined. Results: After adjusting for age and gender, rs1802295 (OR 5.724, P=0.03) and rs231362 (OR=5.683, P=0.016) were found to be associated with T2DM. Triglyceride levels were higher in TT and CT carriers for rs16861329 (1.05 (0.8-1.34) mmol/l) than in CC carriers (0.91 (0.73-1.23) mmol/l) with P=0.008 and that high-density lipoprotein cholesterol (HDL-C) was lower in TT and CT carriers (1.17 (1.02-1.33) mmol/l) than in CC carriers (1.21 (1.05-1.41) mmol/l), with P=0.034. For rs3923113, the HDL-C levels were lower in the GG carriers (1.08 (0.90-1.18) mmol/l) than in the GT+TT carriers (1.21 (1.04-1.38) mmol/l), with P=0.018. Ours is the first report of this association. Conclusion: rs231362-KCNQ1 and rs1802295-VPS26A are associated with T2DM in the Chinese population. The remaining three SNPs are associated with other aspects of lipid metabolism.

scholarly journals Structural basis of ethnic-specific variants of PAX4 associated with type 2 diabetes

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jun Hosoe ◽  
Ken Suzuki ◽  
Fuyuki Miya ◽  
Takashi Kato ◽  
Tatsuhiko Tsunoda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structural Analysis ◽  
Japanese Population ◽  
Association Studies ◽  
Genome Wide Association ◽  
Structural Basis ◽  
Genome Wide Association Studies ◽  
Risk Variants ◽  
Genome Wide

AbstractRecently, we conducted genome-wide association studies of type 2 diabetes (T2D) in a Japanese population, which identified 20 novel T2D loci that were not associated with T2D in Europeans. Moreover, nine novel missense risk variants, such as those of PAX4, were not rare in the Japanese population, but rare in Europeans. We report in silico structural analysis of ethnic-specific variants of PAX4, which suggests the pathogenic effect of these variants.

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