Progress in Understanding Type 1 Diabetes Through Its Genetic Overlap with Other Autoimmune Diseases

Roizen, Jeffrey D.; Bradfield, Jonathan P.; Hákonarson, Hákon

doi:10.1007/s11892-015-0668-4

Cited by 21 publications

(13 citation statements)

References 48 publications

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“…Although these conditions have distinct symptoms, previous findings have shown strong evidence that complex interactions occur between these diseases as a result of shared genetic architecture. 48 , 49 The identification of these previously known findings regarding these autoimmune diseases provides support for the network approach of investigating cross-phenotype associations derived from PheWASs.…”

Section: Discussionmentioning

confidence: 74%

Human-Disease Phenotype Map Derived from PheWAS across 38,682 Individuals

Verma

Bang²,

Miller

et al. 2019

The American Journal of Human Genetics

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Phenome-wide association studies (PheWASs) have been a useful tool for testing associations between genetic variations and multiple complex traits or diagnoses. Linking PheWAS-based associations between phenotypes and a variant or a genomic region into a network provides a new way to investigate cross-phenotype associations, and it might broaden the understanding of genetic architecture that exists between diagnoses, genes, and pleiotropy. We created a network of associations from one of the largest PheWASs on electronic health record (EHR)-derived phenotypes across 38,682 unrelated samples from the Geisinger’s biobank; the samples were genotyped through the DiscovEHR project. We computed associations between 632,574 common variants and 541 diagnosis codes. Using these associations, we constructed a “disease-disease” network (DDN) wherein pairs of diseases were connected on the basis of shared associations with a given genetic variant. The DDN provides a landscape of intra-connections within the same disease classes, as well as inter-connections across disease classes. We identified clusters of diseases with known biological connections, such as autoimmune disorders (type 1 diabetes, rheumatoid arthritis, and multiple sclerosis) and cardiovascular disorders. Previously unreported relationships between multiple diseases were identified on the basis of genetic associations as well. The network approach applied in this study can be used to uncover interactions between diseases as a result of their shared, potentially pleiotropic SNPs. Additionally, this approach might advance clinical research and even clinical practice by accelerating our understanding of disease mechanisms on the basis of similar underlying genetic associations.

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Section: Discussionmentioning

confidence: 74%

Human-Disease Phenotype Map Derived from PheWAS across 38,682 Individuals

Verma

Bang²,

Miller

et al. 2019

The American Journal of Human Genetics

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“…Type 1 DM is the result of an autoimmune process with destruction of the insulin-producing beta cells of the pancreas. In contrast, various pathophysiologic processes contribute to type 2 DM including varying degrees of insulin resistance and relative insulin deficiency [7][8][9][10][11]. The clinical features of DM may be modified by genetic or environmental influences.…”

Section: Discussionmentioning

confidence: 99%

Thiazide-Induced Hyperglycemia in a 6 Years Old Girl: A Case Report and Review of the Literature

Walia

Tobias

2016

J Med Cases

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Various factors may affect glucose homeostasis in children resulting in rare clinical scenarios. Alterations in glucose regulation and hyperglycemia may result from pharmacologic interventions and the introduction of new medications. Although used most commonly to control fluid balance, an uncommon adverse effect of the thiazide diuretics is hyperglycemia. We present a 6-year-old girl with congenital heart disease who developed clinically significant hyperglycemia when a thiazide diuretic was added to her medication regimen. Previous reports of similar responses are reviewed, physiologic mechanisms are postulated, and treatment strategies are proposed.

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“…To wit, although there is a high degree of overlap in involved variants in autoimmune diseases with similar pathophysiology, in disease with differing pathophysiology (eg, DM and IBD), the same variants are often implicated in opposite roles. 73 Further, even in diseases with differing pathophysiology and many non-overlapping variants and oppositely implicated shared variants, variants which are overlapping or shared still exist. 73 This is to say, for now, the addition of autoimmune diseases to the Diabetes Syndrome framework is not warranted until we understand more.…”

Section: The Diabetes Syndrome As a Conceptual Frameworkmentioning

confidence: 99%

The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

Rachfal¹,

Grant²,

Schwartz³

2021

IJGM

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The four basic pathophysiologic mechanisms which damage the β-cell within diabetes (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance [IR]) also contribute to cell and tissue damage and elevate the risk of developing all typical diabetes-related complications. Genetic susceptibility to damage from abnormal external and internal environmental factors has been described including inflammation and IR. All these mechanisms can promote epigenetic changes, and in total, these pathophysiologic mechanisms interact and react with each other to cause damage to cells and tissues ultimately leading to disease. Importantly, these pathophysiologic mechanisms also serve to link other common conditions including cancer, dementia, psoriasis, atherosclerotic cardiovascular disease (ASCVD), nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). The "Diabetes Syndrome", an overarching group of interrelated conditions linked by these overlapping mechanisms, can be viewed as a conceptual framework that can facilitate understanding of the interrelationships of superficially disparate conditions. Recognizing the association of the conditions within the Diabetes Syndrome due to common pathophysiologies has the potential to provide both benefit to the patient (eg, prevention, early detection, precision medicine) and to the advancement of medicine (eg, driving education, research, and dynamic decision-based medical practice).

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Progress in Understanding Type 1 Diabetes Through Its Genetic Overlap with Other Autoimmune Diseases

Cited by 21 publications

References 48 publications

Human-Disease Phenotype Map Derived from PheWAS across 38,682 Individuals

Human-Disease Phenotype Map Derived from PheWAS across 38,682 Individuals

Thiazide-Induced Hyperglycemia in a 6 Years Old Girl: A Case Report and Review of the Literature

The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

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