ArticleDiabetologia2012
Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The sequenced rat brain transcriptome--its use in identifying networks predisposing alcohol consumption.The FEBS journal · 2015Pooled it
- Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease.PLoS genetics · 2014Pooled it
- Genetic variation at glucose and insulin trait loci and response to glucose-insulin-potassium (GIK) therapy: the IMMEDIATE trial.The pharmacogenomics journal · 2015Trial
- Interpreting Functional Impact of Genetic Variations by Network QTL for Genotype-Phenotype Association Study.Frontiers in cell and developmental biology · 2021Article
- Peroxiredoxins and Immune Infiltrations in Colon Adenocarcinoma: Their Negative Correlations and Clinical Significances, an In Silico Analysis.Journal of Cancer · 2020Article
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- Gene Expression Meta-Analysis of Seven Candidate Gene Sets for Diabetes Traits Following a GWAS Pathway Study.Frontiers in genetics · 2018Article
- Voltage-gated calcium channels: Novel targets for cancer therapy.Oncology letters · 2017Article
- Functional regression method for whole genome eQTL epistasis analysis with sequencing data.BMC genomics · 2017Article
- The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.BMC systems biology · 2016Article
- Consensus Genome-Wide Expression Quantitative Trait Loci and Their Relationship with Human Complex Trait Disease.Omics : a journal of integrative biology · 2016Article
- Integrative network analysis reveals different pathophysiological mechanisms of insulin resistance among Caucasians and African Americans.BMC medical genomics · 2015Article
- Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored Therapies?PPAR research · 2015Review
- Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis.BMC medical genomics · 2014Article
- Expression quantitative trait analyses to identify causal genetic variants for type 2 diabetes susceptibility.World journal of diabetes · 2014Review
- Biomarkers for combat-related PTSD: focus on molecular networks from high-dimensional data.European journal of psychotraumatology · 2014Article
- Alternative Approaches in Gene Discovery and Characterization in Alzheimer's Disease.Current genetic medicine reports · 2013Article
- Systems Biology Approaches and Applications in Obesity, Diabetes, and Cardiovascular Diseases.Current cardiovascular risk reports · 2013Article
- eQTL Epistasis - Challenges and Computational Approaches.Frontiers in genetics · 2013Article
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Authors and funding
7 authors.
Funding
Abstract
aims/hypothesisWhile genome-wide association studies (GWASs) have been successful in identifying novel variants associated with various diseases, it has been much more difficult to determine the biological mechanisms underlying these associations. Expression quantitative trait loci (eQTL) provide another dimension to these data by associating single nucleotide polymorphisms (SNPs) with gene expression. We hypothesised that integrating SNPs known to be associated with type 2 diabetes with eQTLs and coexpression networks would enable the discovery of novel candidate genes for type 2 diabetes.
methodsWe selected 32 SNPs associated with type 2 diabetes in two or more independent GWASs. We used previously described eQTLs mapped from genotype and gene expression data collected from 1,008 morbidly obese patients to find genes with expression associated with these SNPs. We linked these genes to coexpression modules, and ranked the other genes in these modules using an inverse sum score.
resultsWe found 62 genes with expression associated with type 2 diabetes SNPs. We validated our method by linking highly ranked genes in the coexpression modules back to SNPs through a combined eQTL dataset. We showed that the eQTLs highlighted by this method are significantly enriched for association with type 2 diabetes in data from the Wellcome Trust Case Control Consortium (WTCCC, p = 0.026) and the Gene Environment Association Studies (GENEVA, p = 0.042), validating our approach. Many of the highly ranked genes are also involved in the regulation or metabolism of insulin, glucose or lipids. CONCLUSIONS/
interpretationWe have devised a novel method, involving the integration of datasets of different modalities, to discover novel candidate genes for type 2 diabetes.
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