scholarly journals Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

2014 ◽  
Vol 46 (3) ◽  
pp. 234-244 ◽  
Author(s):  
Anubha Mahajan ◽  
◽  
Min Jin Go ◽  
Weihua Zhang ◽  
Jennifer E Below ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Architecture ◽  
Meta Analysis ◽  
Diabetes Susceptibility ◽  
Genome Wide ◽  
Insight Into

scholarly journals Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis

2020 ◽  
Vol 8 (1) ◽  
pp. e001140
Author(s):  
Xinpei Wang ◽  
Jinzhu Jia ◽  
Tao Huang
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Correlation ◽  
Genetic Architecture ◽  
Large Scale ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Shared Genetic

ObjectiveWe aimed to estimate genetic correlation, identify shared loci and test causality between leptin levels and type 2 diabetes (T2D).Research design and methodsOur study consists of three parts. First, we calculated the genetic correlation of leptin levels and T2D or glycemic traits by using linkage disequilibrium score regression analysis. Second, we conducted a large-scale genome-wide cross-trait meta-analysis using cross-phenotype association to identify shared loci between trait pairs that showed significant genetic correlations in the first part. In the end, we carried out a bidirectional MR analysis to find out whether there is a causal relationship between leptin levels and T2D or glycemic traits.ResultsWe found positive genetic correlations between leptin levels and T2D (Rg=0.3165, p=0.0227), fasting insulin (FI) (Rg=0.517, p=0.0076), homeostasis model assessment-insulin resistance (HOMA-IR) (Rg=0.4785, p=0.0196), as well as surrogate estimates of β-cell function (HOMA-β) (Rg=0.4456, p=0.0214). We identified 12 shared loci between leptin levels and T2D, 1 locus between leptin levels and FI, 1 locus between leptin levels and HOMA-IR, and 1 locus between leptin levels and HOMA-β. We newly identified eight loci that did not achieve genome-wide significance in trait-specific genome-wide association studies. These shared genes were enriched in pancreas, thyroid gland, skeletal muscle, placenta, liver and cerebral cortex. In addition, we found that 1-SD increase in HOMA-IR was causally associated with a 0.329 ng/mL increase in leptin levels (β=0.329, p=0.001).ConclusionsOur results have shown the shared genetic architecture between leptin levels and T2D and found causality of HOMA-IR on leptin levels, shedding light on the molecular mechanisms underlying the association between leptin levels and T2D.

scholarly journals Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

PLoS Genetics ◽  
2014 ◽  
Vol 10 (8) ◽  
pp. e1004517 ◽  
Author(s):  
Maggie C. Y. Ng ◽  
Daniel Shriner ◽  
Brian H. Chen ◽  
Jiang Li ◽  
Wei-Min Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
African Americans ◽  
Genetic Architecture ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Recessive Genome-wide Meta-analysis Illuminates Genetic Architecture of Type 2 Diabetes

Diabetes ◽  
2021 ◽  
pp. db210545
Author(s):  
Mark J. O'Connor ◽  
Philip Schroeder ◽  
Alicia Huerta-Chagoya ◽  
Paula Cortés-Sánchez ◽  
Silvía Bonàs-Guarch ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Architecture ◽  
Meta Analysis ◽  
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 Genome-Wide Association Study Identifies a Novel Locus Contributing to Type 2 Diabetes Susceptibility in Sikhs of Punjabi Origin From India

Diabetes ◽  
2013 ◽  
Vol 62 (5) ◽  
pp. 1746-1755 ◽  
Author(s):  
R. Saxena ◽  
D. Saleheen ◽  
L. F. Been ◽  
M. L. Garavito ◽  
T. Braun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Diabetes Susceptibility ◽  
Genome Wide

Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies

2008 ◽  
Vol 46 (3) ◽  
pp. 217-226 ◽  
Author(s):  
Stephanie-May Ruchat ◽  
Cathy E. Elks ◽  
Ruth J. F. Loos ◽  
Marie-Claude Vohl ◽  
S. John Weisnagel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Diabetes Susceptibility ◽  
Genome Wide
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