Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes.

Diabetologia
H P KangA J Butte

Abstract

While 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. We 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. We 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 enri...Continue Reading

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Citations

Jul 18, 2014·PLoS Genetics·Ville-Petteri MäkinenThemistocles L Assimes
Mar 14, 2013·Current Genetic Medicine Reports·Nilüfer Ertekin-TanerDavid A Bennett
Jan 18, 2013·Current Cardiovascular Risk Reports·Qingying MengXia Yang
Jul 20, 2016·Omics : a Journal of Integrative Biology·Chen-Hsin YuJohn Moult
Sep 25, 2016·BMC Systems Biology·Jason E McDermottKatrina M Waters
Oct 3, 2013·Journal of Molecular Endocrinology·A StevensM J Dunne
Aug 7, 2017·Oncology Letters·Nam Nhut PhanYen-Chang Lin

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Methods Mentioned

BETA
gastric bypass

Software Mentioned

GENEVA

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