Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetics of type 2 diabetes: insights into the pathogenesis and its clinical application.

ABSTRACT: With rapidly increasing prevalence, diabetes has become one of the major causes of mortality worldwide. According to the latest studies, genetic information makes substantial contributions towards the prediction of diabetes risk and individualized antidiabetic treatment. To date, approximately 70 susceptibility genes have been identified as being associated with type 2 diabetes (T2D) at a genome-wide significant level (P < 5 × 10(-8)). However, all the genetic loci identified so far account for only about 10% of the overall heritability of T2D. In addition, how these novel susceptibility loci correlate with the pathophysiology of the disease remains largely unknown. This review covers the major genetic studies on the risk of T2D based on ethnicity and briefly discusses the potential mechanisms and clinical utility of the genetic information underlying T2D.

SUBMITTER: Sun X

PROVIDER: S-EPMC4016836 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genetics of type 2 diabetes: insights into the pathogenesis and its clinical application.

Sun Xue X Yu Weihui W Hu Cheng C

BioMed research international 20140417

With rapidly increasing prevalence, diabetes has become one of the major causes of mortality worldwide. According to the latest studies, genetic information makes substantial contributions towards the prediction of diabetes risk and individualized antidiabetic treatment. To date, approximately 70 susceptibility genes have been identified as being associated with type 2 diabetes (T2D) at a genome-wide significant level (P < 5 × 10(-8)). However, all the genetic loci identified so far account for ...[more]

PMID: 24864266

Similar Datasets

Genetics, pathogenesis and clinical interventions in type 1 diabetes.

Project description:Type 1 diabetes is an autoimmune disorder afflicting millions of people worldwide. Once diagnosed, patients require lifelong insulin treatment and can experience numerous disease-associated complications. The last decade has seen tremendous advances in elucidating the causes and treatment of the disease based on extensive research both in rodent models of spontaneous diabetes and in humans. Integrating these advances has led to the recognition that the balance between regulatory and effector T cells determines disease risk, timing of disease activation, and disease tempo. Here we describe current progress, the challenges ahead and the new interventions that are being tested to address the unmet need for preventative or curative therapies.

| S-EPMC4959889 | biostudies-literature

Genetics of Type 2 Diabetes and Clinical Utility.

Project description:A large proportion of heritability of type 2 diabetes (T2D) has been attributed to inherent genetics. Recent genetic studies, especially genome-wide association studies (GWAS), have identified a multitude of variants associated with T2D. It is thus reasonable to question if these findings may be utilized in a clinical setting. Here we briefly review the identification of risk loci for T2D and discuss recent efforts and propose future work to utilize these loci in clinical setting-for the identification of individuals who are at particularly high risks of developing T2D and for the stratification of specific health-care approaches for those who would benefit most from such interventions.

| S-EPMC4488669 | biostudies-literature

Genetics Insights in the Relationship Between Type 2 Diabetes and Coronary Heart Disease.

Project description:Diabetes mellitus is a major risk factor for coronary heart disease (CHD). The major form of diabetes mellitus is type 2 diabetes mellitus (T2D), which is thus largely responsible for the CHD association in the general population. Recent years have seen major advances in the genetics of T2D, principally through ever-increasing large-scale genome-wide association studies. This article addresses the question of whether this expanding knowledge of the genomics of T2D provides insight into the etiologic relationship between T2D and CHD. We will investigate this relationship by reviewing the evidence for shared genetic loci between T2D and CHD; by examining the formal testing of this interaction (Mendelian randomization studies assessing whether T2D is causal for CHD); and then turn to the implications of this genetic relationship for therapies for CHD, for therapies for T2D, and for therapies that affect both. In conclusion, the growing knowledge of the genetic relationship between T2D and CHD is beginning to provide the promise for improved prevention and treatment of both disorders.

| S-EPMC7250006 | biostudies-literature

Genetics of idiopathic inflammatory myopathies: insights into disease pathogenesis.

Project description:Purpose of reviewTo review the advances that have been made in our understanding of the genetics of idiopathic inflammatory myopathies (IIM) in the past 2 years, with a particular focus on dermatomyositis and polymyositis.Recent findingsFine-mapping studies in the major histocompatibility complex region in Caucasian and Korean populations have identified novel human leukocyte antigen (HLA) variants that are associated with autoantibody subgroups in IIM. Differences in HLA associations have been identified between Caucasian adult-onset and juvenile-onset patients with anti-TIF1 autoantibodies, suggesting distinct aetiologies in these patients. For some autoantibodies, the strongest associations identified are specific amino acid positions within HLA molecules, providing mechanistic insights into disease pathogenesis.A meta-analysis combining data from four seropositive rheumatic diseases identified 22 novel non-HLA associations in IIM, of which seven were previously reported at suggestive significance in IIM. A genome-wide association study conducted in the Japanese population identified a significant association with WDFY4 in patients with clinically amyopathic dermatomyositis.SummaryConsiderable progress has been made in understanding the genetics of IIM, including differences in clinical and autoantibody subgroups. As research continues, there should be a focus to increase statistical strength and precision by conducting meta-analyses and trans-ethnic studies.

| S-EPMC6791565 | biostudies-literature

Genetics of type 2 diabetes.

Project description:To provide an overview of the genetics of type 2 diabetes in the context of recent progress in the understanding of the genetic architecture of the disease and its applicability to the pathogenesis of the disease as well as efforts to individualize therapy in type 2 diabetes. Efforts are underway to understand how these loci alter measurable physiologic processes in nondiabetic humans. However, it is important to understand the potential pitfalls in such studies and the limitations underlying measurement of insulin secretion and action using qualitative methodologies.The availability of large population-based cohorts and the ease with which large numbers of common genetic variants can be genotyped has enabled the discovery of multiple loci and pathways associated with type 2 diabetes. Recent efforts examining quantitative traits such as fasting glucose concentrations have led to the discovery of other genes likely to be important in the development of diabetes.The past 4 years have witnessed a significant increase in our understanding of genetic predisposition to type 2 diabetes. Hopefully more progress will be made in applying this knowledge to the pathophysiology of type 2 diabetes in the coming years.

| S-EPMC2953639 | biostudies-literature

Genetics of type 1 diabetes.

Project description:BACKGROUND:Type 1 diabetes, a multifactorial disease with a strong genetic component, is caused by the autoimmune destruction of pancreatic ? cells. The major susceptibility locus maps to the HLA class II genes at 6p21, although more than 40 non-HLA susceptibility gene markers have been confirmed. CONTENT:Although HLA class II alleles account for up to 30%-50% of genetic type 1 diabetes risk, multiple non-MHC loci contribute to disease risk with smaller effects. These include the insulin, PTPN22, CTLA4, IL2RA, IFIH1, and other recently discovered loci. Genomewide association studies performed with high-density single-nucleotide-polymorphism genotyping platforms have provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remain to be performed. Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years. Genetic risk for type 1 diabetes can be further stratified by selection of children with susceptible genotypes at other diabetes genes, by selection of children with a multiple family history of diabetes, and/or by selection of relatives that are HLA identical to the proband. SUMMARY:Children with the HLA-risk genotypes DR3/4-DQ8 or DR4/DR4 who have a family history of type 1 diabetes have more than a 1 in 5 risk for developing islet autoantibodies during childhood, and children with the same HLA-risk genotype but no family history have approximately a 1 in 20 risk. Determining extreme genetic risk is a prerequisite for the implementation of primary prevention trials, which are now underway for relatives of individuals with type 1 diabetes.

| S-EPMC4874193 | biostudies-literature

Genetics of type 1 diabetes.

Project description:Type 1 diabetes (T1D) results from immune-mediated loss of pancreatic beta cells leading to insulin deficiency. It is the most common form of diabetes in children, and its incidence is on the rise. This article reviews the current knowledge on the genetics of T1D. In particular, we discuss the influence of HLA and non-HLA genes on T1D risk and disease progression through the preclinical stages of the disease, and the development of genetic scores that can be applied to disease prediction. Racial/ethnic differences, challenges and future directions in the genetics of T1D are also discussed.

| S-EPMC5918237 | biostudies-literature

New insights into the pathogenesis and genetics of psoriatic arthritis.

Project description:Psoriasis vulgaris and psoriatic arthritis (PsA) are inter-related heritable diseases. Psoriatic skin is characterized by hyperproliferative, poorly differentiated keratinocytes and severe inflammation. Psoriatic joints are characterized by highly inflamed synovia and entheses with focal erosions of cartilage and bone. Genetic analyses have uncovered risk factors shared by both psoriasis and PsA. Predisposition to psoriasis and PsA arising from common variation is most strongly conferred by the HLA class I region. Other genetic risk factors implicate the interleukin (IL)-23 pathway and the induction and regulation of type 17 T-helper cells in the pathogenesis of both diseases. Secretion of cytokines, such as IL-22 and IL-17, could result in the hyperproliferative phenotype of keratinocytes and potentially synoviocytes, leading to a vicious cycle of cellular proliferation and inflammation in both the skin and joints. In synovial tissue, disease-related cytokines could also promote osteoclast formation, resulting in bone erosion. The next step will be to identify genetic risk factors specifically associated with PsA. Although therapies that target tumor necrosis factor are often highly successful in the treatment of both diseases, genetic findings are likely to lead to the development of treatments tailored to an individual's genetic profile.

| S-EPMC2790861 | biostudies-literature

Enteroviral infections in the pathogenesis of type 1 diabetes: new insights for therapeutic intervention.

Project description:The development of islet autoimmunity and type 1 diabetes has long been linked with enteroviral infection but a causal relationship has proven hard to establish. This is partly because much of the epidemiological evidence derives from studies of neutralising antibody generation in blood samples while less attention has been paid to the pancreatic beta cell as a site of infection. Nevertheless, recent studies have revealed that beta cells express specific enteroviral receptors and that they can sustain a productive enteroviral infection. Importantly, they can also mount antiviral responses which attenuate viral replication and may favour the establishment of a persistent enteroviral infection. Together, these responses combine to create the Trojan horse by which enteroviruses might precipitate islet autoimmunity.

| S-EPMC6294842 | biostudies-literature

Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008.

Project description:ContextOver the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear.Evidence acquisitionPrimary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts.Evidence synthesisAs many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications.ConclusionsAlthough substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.

| S-EPMC2626447 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data