Genetic factors in the etiology of type 2 diabetes: linkage analyses, candidate gene association, and genome-wide association and #8211; still a long way to go!

Abstract

Type 2 diabetes is a complex and pleomorphic metabolic disorder arising from a complex interaction between genes and the environment. During the last decade there has been an outpouring of studies providing clues into the genetic architecture underlying type 2 diabetes mellitus. This review provides an overview of the genetics of type 2 diabetes in the context of recent progress in the understanding of the genetic susceptibility of the disease. Approximately 40 variants have been identified so far and the identification of these susceptibility loci for diabetes has introduced novel genes, pathways and mechanisms of diabetes pathogenesis. The genetic loci so far identified account for only a small fraction (approximately 10%) of the overall heritable risk for type 2 diabetes mellitus. Uncovering the missing heritability is essential to the progress of type 2 diabetes genetic studies and to the translation of genetic information into clinical practice. However, it may be a long time before all the susceptibility genes are found. It may take even more time before their roles in different pathways have been elucidated and the mechanisms involved in their interaction with other factors in the disease etiology clarified.

Targets of drugs are generally and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

“…Mutated genes and their corresponding proteins in colorectal cancer and in type-2 diabetes were obtained from the Cancer Gene Census database 48 (Suppl. Table 7) and from the article of Parchwani et al 49 (Suppl. Table 8), respectively.…”

“…Genes involved in colorectal cancer were collected from the Cancer Gene Census 48 database, by selecting those proteins in the entire database that contained the word ‘colorectal’ in their ‘Tumour Types’ column. Genes related to type 2 diabetes were obtained from the article of Parchwani et al 49 . The 18 genes involved in colorectal cancer and the 46 genes related to type 2 diabetes were then mapped to proteins marked by UniProt ID 54 with the help of the Protein Identifier Cross-Reference (PICR) 55 application.…”

“…The human interactome containing 12,439 proteins and 174,666 edges was built from the STRING database 46 . Colorectal cancer- and type 2 diabetes-related proteins were obtained from the Cancer Gene Census database 48 and from the article of Parchwani et al 49 , respectively. Silencing times were calculated separately for every protein with the Turbine program 35 as described in the Methods section using a starting energy of 1,000 and a dissipation value of 5 units.…”

“…The human interactome containing 12,439 proteins and 174,666 edges was built from the STRING database 46 . Colorectal cancer-related proteins were obtained from the Cancer Gene Census database 48 , type 2 diabetes-related proteins were obtained from the article of Parchwani et al 49 . Statistical analysis was performed using the Wilcoxon rank sum (Mann-Whitney) test function of the R package 56 .…”

“…Human interactome containing 12,439 proteins and 174,666 edges was built from the STRING database 46 , 1,726 human drug targets were obtained from the DrugBank database 47 and 99,423 drug-side effect pairs were taken from the SIDER database 2 . Colorectal cancer- and type 2 diabetes-related proteins were obtained from the Cancer Gene Census database 48 and from the article of Parchwani et al 49 , respectively. We used the mean values and the t-test because of the near-normal distribution of the average network distances.…”