Heritability Of Diabetes Type 2

Genetics Of Type 2 Diabetes

Chapter 14 in Diabetes in America, 3rd ed. NIH Pub No. 17-1468, 2017, p. 14.114.25 Type 2 diabetes is thought to result from a combination of environmental, behavioral, and genetic factors, with the heritability of type 2 diabetes estimated to be in the range of 25% to 72% based on family and twin studies. Since early 2007, genomewide association studies (GWAS) have led to an explosion of data for the genetics of type 2 diabetes and related traits. These GWAS have occurred on the background of genotyping arrays populated by common single nucleotide polymorphisms (SNPs), deployed in various cohorts that have coalesced to form large international consortia. As a result, a list of genetic loci that influence type 2 diabetes and quantitative glycemic traits has begun to accumulate. Over 100 type 2 diabetes-associated loci have been identified, in addition to others involved in determining quantitative glycemic traits, such as insulin resistance. However, no variant that is widely shared across populations has been found to have a stronger effect than the rs7903146 SNP in TCF7L2, which itself has only a modest effect (odds ratio ~1.4). Nonetheless, GWAS findings have illustrated novel pathways, pointed toward fundamental biology, drawn attention to the role of beta cell dysfunction in type 2 diabetes, confirmed prior epidemiologic observations, and provided possible targets for pharmacotherapy and pharmacogenetic clinical trials. On the other hand, the causal variants have only been identified for a handful of these loci, a substantial proportion of the heritability of these phenotypes remains unexplained, and this has tempered expectations with regard to their use in clinical prediction. Together, the approximately 100 loci associated with type 2 diabetes thus far explain Continue reading >>

Genetic Screening For The Risk Of Type 2 Diabetes

The prevalence and incidence of type 2 diabetes, representing >90% of all cases of diabetes, are increasing rapidly throughout the world. The International Diabetes Federation has estimated that the number of people with diabetes is expected to rise from 366 million in 2011 to 552 million by 2030 if no urgent action is taken. Furthermore, as many as 183 million people are unaware that they have diabetes (www.idf.org). Therefore, the identification of individuals at high risk of developing diabetes is of great importance and interest for investigators and health care providers. Type 2 diabetes is a complex disorder resulting from an interaction between genes and environment. Several risk factors for type 2 diabetes have been identified, including age, sex, obesity and central obesity, low physical activity, smoking, diet including low amount of fiber and high amount of saturated fat, ethnicity, family history, history of gestational diabetes mellitus, history of the nondiabetic elevation of fasting or 2-h glucose, elevated blood pressure, dyslipidemia, and different drug treatments (diuretics, unselected β-blockers, etc.) (1–3). There is also ample evidence that type 2 diabetes has a strong genetic basis. The concordance of type 2 diabetes in monozygotic twins is ~70% compared with 20–30% in dizygotic twins (4). The lifetime risk of developing the disease is ~40% in offspring of one parent with type 2 diabetes, greater if the mother is affected (5), and approaching 70% if both parents have diabetes. In prospective studies, we have demonstrated that first-degree family history is associated with twofold increased risk of future type 2 diabetes (1,6). The challenge has been to find genetic markers that explain the excess risk associated with family history of diabetes Continue reading >>

Heritability - Snpedia

Heritability is defined as the degree to which individual genetic variation accounts for phenotypic variation seen in a population. In a scientifically sloppy sense, it's somewhat (mis)used to give a sense of what proportion of your risk for a given disease is derived from your genes (as opposed to non-genetic influences, such as your environment, diet, etc). Wikipedia Most heritability estimates have been based on family (and twin) studies. An approach developed more recently ([ PMID 25383972 ]) estimates heritability based on unrelated individuals of mixed ethnic ("admixed") backgrounds. This approach appears to indicate lower heritability than is estimated from twin studies; for example, heritability estimates for height and body mass index are 0.55 and 0.23, respectively, compared to the ~0.80 and ~0.50 estimates from twin studies. If heritability is lower than classically thought, the proportion of genetic variance explained by SNP studies is actually significantly higher - relatively common SNPs may explain most genetic variation. It is important to remember that high heritability does not imply that a trait or disease is inevitable. In fact, some highly heritable traits can be modified by simple changes in the environment. Phenylketonuria (PKU), for example, is a genetic disease with high heritability that can be strongly influenced by a relatively straightforward change in diet (restricting intake of the amino acid phenylalanine). Even if Alzheimer's disease has a relatively high heritability, environmental factors and changes may alter disease progression and severity. Heritability estimates for selected medical conditions present in SNPedia are summarized below; an independent source of information about heritability in humans (as well as other species) can b Continue reading >>

Genetics Of Type 2 Diabetespitfalls And Possibilities

Genetics of Type 2 DiabetesPitfalls and Possibilities Rashmi B. Prasad 1,* and Leif Groop 1,2,* 1Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, CRC, Skne University Hospital SUS, SE-205 02 Malm, Sweden 2Finnish Institute of Molecular Medicine (FIMM), Helsinki University, Helsinki 00014, Finland *Authors to whom correspondence should be addressed; E-Mails: [email protected] (R.B.P.); [email protected] (L.G.). Received 2014 Dec 9; Accepted 2015 Feb 27. Copyright 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( ). This article has been cited by other articles in PMC. Type 2 diabetes (T2D) is a complex disease that is caused by a complex interplay between genetic, epigenetic and environmental factors. While the major environmental factors, diet and activity level, are well known, identification of the genetic factors has been a challenge. However, recent years have seen an explosion of genetic variants in risk and protection of T2D due to the technical development that has allowed genome-wide association studies and next-generation sequencing. Today, more than 120 variants have been convincingly replicated for association with T2D and many more with diabetes-related traits. Still, these variants only explain a small proportion of the total heritability of T2D. In this review, we address the possibilities to elucidate the genetic landscape of T2D as well as discuss pitfalls with current strategies to identify the elusive unknown heritability including the possibility that our definition of diabetes and its subgroups is imprecise and thereby makes the identification of g Continue reading >>

Which Type Of Diabetes Is More Likely To Be Inherited And Why?

Question: Which type of diabetes is more likely to be inherited and why? Answer: Type 1 diabetes typically occurs in childhood, while type 2 diabetes usually develops in adults. However, some adults develop a form of diabetes that looks very similar to type 1 diabetes, and now with the huge increase in obesity, many children and adolescents are getting type 2 diabetes. Now, both type 1 and type 2 diabetes have a genetic component; that means of course, that they tend to run in families. However, we often regard diseases that develop in childhood as being more likely to be due to genetics. But this is not the case for diabetes, and in fact, studies show that type 2, which mostly commonly develops in adulthood, seems to have a greater genetic basis than the childhood form of type 1 diabetes. For example, as you know, identical twins share 100 percent of their genetic material; however, if one twin has type 1 diabetes, the chance of that the other twin will develop it is only 10 to 20 percent. In contrast, if one twin has type 2, or the adult form of diabetes, the other twin has up to a 90 percent chance of developing type 2 diabetes. In type 2 diabetes, we know that overeating and lack of physical activity are very important contributors. Meanwhile, for type 1 diabetes, it's more the exposure to toxins in the environment, possibly viruses, and other external factors that can increase risk to this form of diabetes. Next: What Is The Risk That A Child Will Develop Diabetes If One Or Both Parents Are Diabetic? Previous: What Are The Meanings and Significance Of These Terms Related To Diabetes: 'Beta Cells,' 'Islets,' 'Glucagon,' and 'Amylin'? Continue reading >>

Payperview: Genetics Of Type 2 Diabetes - Karger Publishers

Markku Laakso, MD, PhD, Academy Professor Institute of Clinical Medicine, Internal Medicine University of Eastern Finland and Kuopio University Hospital I have read the Karger Terms and Conditions and agree. Genetic and environmental factors as well as their interactions contribute to the pathogenesis of type 2 diabetes. Linkage analysis, candidate gene approaches, genome-wide association studies, and sequencing have been used in the identification of common, low-frequency and rare variants for type 2 diabetes. Genome-wide association studies have identified >80 common variants for type 2 diabetes, with small effect sizes (risk of type 2 diabetes increased by 5-40%). Almost all of these variants regulate insulin secretion, and only a few regulate insulin sensitivity. Common variants capture only 10% of the heritability of type 2 diabetes. Low-frequency and rare variants with large effects have also been identified, but their contribution to missing heritability' at the population level is limited. Gene-environment and gene-gene interactions and epigenetics are likely to contribute to the missing heritability of type 2 diabetes. Epigenetic factors (DNA methylations and histone modifications) are especially important because they might mediate the effects of environmental exposures on the risk of type 2 diabetes. Although understanding of the genetics of type 2 diabetes has exhibited great progress in the past few years, a substantial amount of additional work will be required to identify causal variants/genes and molecular mechanisms via which the association signals found confer diabetes risk. World Health Organization: Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Geneva: World Health Organization, 1999. International Diabetes Fe Continue reading >>

Heritability Of Quantitative Traits Associated With Type 2 Diabetes Mellitus In Large Multiplex Families From South India

Volume 58, Issue 10 , October 2009, Pages 1439-1445 Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India Author links open overlay panel Rasika A.Mathiasa Get rights and content India is a major contributor to the global public health burden of diabetes. We have undertaken a family study of large multiplex families from Chennai, South India, and report on the familial aggregation of quantitative traits associated with type 2 diabetes mellitus in these pedigrees. Five hundred twenty-four individuals older than 19 years from 26 large multiplex pedigrees were ascertained. Detailed questionnaires and phenotype data were obtained on all participating individuals including fasting blood glucose, fasting insulin, lipid profiles, height, weight, and other anthropometric and clinical measures. Heritability estimates were calculated for all quantitative traits at the univariate level, and bivariate analyses were done to determine the correlation in genetic and environmental control across these quantitative traits. Heritability estimates ranged from 0.21 to 0.72. The heritability estimates for traits most directly related to type 2 diabetes mellitus were 0.24 0.08 for fasting blood glucose and 0.41 0.09 for fasting insulin. In addition, there was evidence for common genetic control for many pairs of these traits. These bivariate analyses suggested common genes for fasting insulin and central obesity measures (body mass index, waist, and hip), with complete genetic correlation between fasting insulin and waist. Quantitative traits associated with type 2 diabetes mellitus have heritabilities suggestive of some familial or genetic effect. The evidence for pleiotropic control of insulin and central obesityrelated t Continue reading >>

Genetics Of Type 2 Diabetes

Omar Ali, Medical College of Wisconsin, Milwaukee, WI 53226, United States Author contributions: Ali O reviewed the published literature and wrote the article in its entirety. Correspondence to: Omar Ali, MD, Medical College of Wisconsin, Milwaukee, 8701 W Watertown Plank Rd, WI 53226, United States. ude.wcm@ilao Telephone: +1-414-2666750 Fax: +1-414-2666749 Received 2013 Mar 3; Revised 2013 Jun 1; Accepted 2013 Jul 18. Copyright 2013 Baishideng Publishing Group Co., Limited. All rights reserved. This article has been cited by other articles in PMC. Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this missing heritability, including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed. Keywords: Type 2 diabetes, Genetics, TCF7L2, Genome-wide association studies, Heritability Core tip: We review the history and the current state of knowledge regarding the genetic component of type 2 diabetes risk. Genes like TCF7L2 that have been replicated in multiple studies are discussed in detail. The signi Continue reading >>

Genetic Epidemiology Of Diabetes

Diabetes is a metabolic condition in which the body fails to produce enough insulin. Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing β cells, which leaves the patient dependent on insulin injections for survival (1) T2D, formerly known as adult-onset diabetes, occurs when impaired insulin effectiveness (insulin resistance) is accompanied by the failure to produce sufficient β cell insulin. Patients can be placed on regimens to reduce weight or manage diet or treated with medication and, less often, insulin injections. This latter form of diabetes accounts for as much as 95% of cases. Gestational diabetes is another form of diabetes, defined as a state of glucose intolerance during pregnancy that usually subsides after delivery but has major implications for subsequent risk of T2D, as pregnancy serves as an “environmental” stressor that reveals a genetic predisposition. Other less common forms of diabetes include the rare, genetically determined disease maturity onset diabetes of the young (MODY), diabetes resulting from surgery, and other illnesses that constitute only 1–5% of cases. Based on plasma glucose measurements, 2 conditions have been identified with increased risk of the disease (2): (a) impaired glucose tolerance (IGT) is defined as hyperglycemia intermediate between normal and diabetic levels following a glucose load; (b) impaired fasting glucose (IFG), like IGT, is associated with increased cardiovascular disease (CVD) and future diabetes. Because complications of diabetes may develop years before overt disease, many consider the disease part of a cluster of CVD risk factors that include hypertension, hyperinsulinemia, dyslipidemia, visceral obesity, hypercoagulability, and microalbuminuria. This collection of risk fac Continue reading >>

Decoding The Genetic Predisposition To Type 2 Diabetes

Decoding the Genetic Predisposition to Type 2 Diabetes Researchers have stumbled upon a type 2 diabetes (T2D) heritability quagmire: Only a fraction of T2D predisposition is shown to be attributed to commonly occurring genetic variants, and yet no evidence to date supports a major involvement of low-frequency variants in T2D susceptibility. Reviewed by Clifton Jackness, MD, Assistant Professor, Hofstra Northwell School of Medicine, New York, NY Through worldwide collaborations and large meta-analyses of genome-wide association studies (GWAS) over the past decade, researchers have been able to identify more than 75 common genetic alleles associated with type 2 diabetes (T2D).1 However, these variants overall explain only about 10% of the T2D genetic risk.2 This observation sparked the GoT2D (Genetics of Type 2 Diabetes) and T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) consortia to explore the influence of infrequent or rare variants on the risk of developing T2D.3 A large-scale, comprehensive sequencing study found that virtually all of the T2D-related variants detected were those commonly occurring across populations and had been previously identified. Whole-genome and exome sequencing yielded little evidence for a major contribution of lower-frequency variants in T2D predisposition. Although certain genomic loci have been correlated with T2D, researchers have yet to clearly implicate the relevant alleles that definitively mediate T2D susceptibility. Lead author Christian Fuchsberger, PhD, and a team of scientists from around the world sequenced exomes (the regions of the human genome that code proteins) from 12,940 individuals, including 6504 with T2D and 6436 without T2D, of European, South Asian, East Asian, H Continue reading >>

Heritability And Type 1 Diabetes

Cause , Celiac Disease , Conditions , Environment , Genetics , Health , Neurological , Obesity | 0 comments Type 1 diabetes has been calculated to be about 88% heritable, while type 2 diabetes has been calculated to be about 26% heritable. But what does that really mean? It is probably more helpful to understand what it does NOT mean. It has nothing to do with how much of your risk for developing diabetes is due to your unalterable genetics. Heritability is defined as the degree to which individual genetic variation accounts for phenotypic variation seen in a population. In a scientifically sloppy sense, it is mis-used to give a sense of what proportion of your risk for a given disease is derived from your genes (as opposed to non-genetic influences, such as your environment, diet, etc). It is important to understand that high heritability does not imply that a trait or disease is inevitable. In fact, some highly heritable traits can be modified by simple changes in the environment. Phenylketonuria (PKU), for example, is a genetic disease with high heritability that can be strongly influenced by a relatively straightforward change in diet (restricting intake of the amino acid phenylalanine). Even if Alzheimers disease has a relatively high heritability, environmental factors and changes may alter disease progression and severity. Heritability estimates for selected medical conditions present in SNPedia are summarized below We consider type 1 diabetes to follow the same pattern as Alzheimers disease, in that it has a relatively high heritability, yet environmental factors and changes may alter disease progression and severity. Heritability is a measure of the relative contribution of genotypic variance, not an analysis of the cause of the trait. A genotypephenotype dist Continue reading >>

Genetics Of Type 2 Diabetes

Until recently the genetic variation and genes involved in type 2 diabetes were very poorly characterised. Traditionally genetic studies focused on the collection and characterisation of multi-generation families but type 2 diabetes occurs in older age, making the collection of affected families difficult – the parents of most patients have died and most offspring have yet to develop the condition. Furthermore the increasing prevalence of type 2 diabetes over one or two generations proves that the changing environment has a strong role to play in type 2 diabetes risk – gene frequencies do not change appreciably in 1 or 2 generations, and certainly not those that influence a disease of largely post reproductive age. Two major developments mean that we now know of 65 regions of the human genome that influence type 2 diabetes risk. First, in 2007 genome wide association studies (GWAS) became possible. These studies provided scientists with the ability to analyse 100,000s of single nucleotide variants (the simplest and most abundant type of DNA marker) in a single experiment. Second, scientists realised that they would have to work together and combine case-control studies to achieve the very large sample sizes that provided adequate statistical power to identify the subtle effects of common genetic risk factors. These developments have resulted in the latest study of 35,000 European type 2 diabetes cases and 115,000 controls.[1] History and heritability of type 2 diabetes genetics. Before trying to identify genes, geneticists tend to perform twin or family studies in attempts to quantify the relative contributions of genes (heritability) and environment. Comparing disease concordance in identical twins to same sex non-identical twins is a powerful approach. However, th Continue reading >>

Is Diabetes Genetic? Facts About Hereditary Risk

Diabetes is a complex set of diseases with no single cause. Genetic factors make some people more vulnerable to diabetes, particularly with the right environment. In addition, certain lifestyle factors can cause type 2 diabetes in individuals with no known family history. This complex interaction between genes, lifestyle, and environment points to the importance of taking steps to minimize individual diabetes risk. Is type 1 diabetes hereditary? Type 1 diabetes is an autoimmune disease, which means that it causes the body's immune system to attack healthy cells. It is often called juvenile diabetes because most people are diagnosed in childhood, and the condition then lasts their lifetime. Doctors used to think type 1 diabetes was wholly genetic. Newer studies have shown, however, that children develop type 1 diabetes 3 percent of the time if their mother has the condition, 5 percent of the time if their father has it, or 8 percent if a sibling has type 1 diabetes. Consequently, researchers now believe that something in the environment has to trigger type 1 diabetes. Some risk factors include: Cold weather. People develop type 1 diabetes in winter more frequently than summer. It is also more common in places with cool climates. Viruses. Researchers think some viruses might activate type 1 diabetes in people who are otherwise vulnerable. Measles, mumps, coxsackie B virus, and rotavirus have been linked to type 1 diabetes. Research suggests that people who develop type 1 diabetes may have autoimmune antibodies in their blood for many years before showing symptoms. As a result, the disease may develop over time, or something may have to activate the autoimmune antibodies for symptoms to appear. Is type 2 diabetes hereditary? Type 2 diabetes is the more common form of the d Continue reading >>

More Type 2 Diabetes Genes Found

Doctors are closer to building a DNA profile of people who are at risk from diabetes after pinpointing another set of genes associated with the disease, reported The Daily Telegraph . The study behind the news report combined the results from several genome-wide association studies, which compared the DNA of thousands of people with type 2 diabetes to that from people without the disease. In addition to confirming several genetic variants that the previous study had associated with the disease, the research identified 12 new variants, bringing the number of linked genes to 38. This well-conducted research has generally been accurately reported by the press. It furthers our understanding of the genetic variations that may increase the risk of type 2 diabetes. These findings are important, but having all of these gene variants does not mean a person will definitely develop the disease. This advance inunlikely to have any immediate implication for screening or prevention of type 2 diabetes. Being overweight or obese isa known modifiable risk factor for this disease. The study was carried out by researchers from a variety of international academic and medical institutions, including the University of Oxford and the Wellcome Trust Sanger Institute in the UK. The research was financially supported by many organisations, including the Academy of Finland, the American Diabetes Association, manufacturers and national research councils. The study was published in the peer-reviewed journal Nature Genetics. The news coverage of this research is clear, explaining that the discovery increases the understanding of the genetic risk factors for developing type 2 diabetes. This was a meta-analysis (statistical pooling) of data from several genome-wide association studies. The researcher Continue reading >>

Heritability And Familiality Of Type 2 Diabetes And Related Quantitative Traits In The Botnia Study

Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland. Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance component model (SOLAR). In addition, family means of these traits and their distribution across families are calculated. The strongest heritability for type 2 diabetes was seen in patients with age at onset 3560years (h 2 = 0.69). However, including patients with onset up to 75years dropped the h 2 estimates to 0.31. Among quantitative traits, the highest h 2 estimates in all individuals and in non-diabetic individuals were seen for lean body mass (h 2 = 0.530.65), HDL-cholesterol (0.520.61) and suppression of NEFA during OGTT (0.630.76) followed by measures of insulin secretion (insulinogenic index [IG30] = 0.410.50) and insulin action (insulin sensitivity index [ISI] = 0.370.40). In contrast, physical activity showed rather low heritability (0.160.18), whereas smoking showed strong heritability (0.570.59). Family means of these traits differed two- to fivefold between families belonging to the lowest and highest quartile of the trait (p < 0.00001). To detect stronger genetic effects in type 2 diabetes, it seems reasonable to restrict inclusion of patients to those with age at onset 3560years. Sequencing of families with extreme quantitative traits could be an important next step in the dissection of the genetics of type 2 diabetes. FamiliesHeritabilityQuantitative traitsType 2 diabetes The online version of t Continue reading >>