Scientists May Be Close To Finding Genetic Cause Of Type 2 Diabetes
Scientists may be close to finding genetic cause of type 2 diabetes Of the 111 chromosome locations identified, 93 percent were found in African-American and European populations. By Amy Wallace|May 8, 2017 at 2:10 PM May 8 (UPI) -- Researchers at University College London report they are closer to unlocking the genetic causes of type 2 diabetes by identifying 111 new chromosome locations, or loci, on the human genome. Type 2 diabetes is one of the most widespread metabolic disorders in the world. Previous studies had identified only 76 loci, and very few of these loci were found in the African-American population, where type 2 diabetes is twice as prevalent as in U.S. descendants of European ancestry. Along with colleagues at Imperial College London, UCL researchers found 93 loci of the additional 111 were found in both African-American and European populations and just 18 are European specific. The study found that the additional 111 loci and previously known 76 loci regulate the expression of at least 266 genes that are next to the identified disease loci. The majority were found outside of gene coding regions but coincided with regulatory "hotspots" that change the expression of the genes in body fat. Studies are being conducted to determine whether these loci alter the expression of the same genes in other tissues such as the pancreas, liver and skeletal muscle associated with type 2 diabetes. "No disease with a genetic predisposition has been more intensely investigated than type 2 diabetes," Dr. Nikolas Maniatis of UCL Genetics, Evolution and Environment department, said in a press release . "We've proven the benefits of gene mapping to identify hundreds of locations where causal mutations might be across many populations, including African-Americans. This provi Continue reading >>
Is Type 2 Diabetes Caused By Genetics?
Diabetes is a complex condition. Several factors must come together for you to develop type 2 diabetes. For example, obesity and a sedentary lifestyle play a role. Genetics can also influence whether you’ll get this disease. If you’ve been diagnosed with type 2 diabetes, there’s a good chance that you’re not the first person with diabetes in your family. According to the American Diabetes Association, your risk of developing type 2 diabetes is: 1 in 7 if one of your parents was diagnosed before the age of 50 1 in 13 if one of your parents was diagnosed after the age of 50 1 in 2, or 50 percent, if both your parents have diabetes Several gene mutations have been linked to the development of type 2 diabetes. These gene mutations can interact with the environment and each other to further increase your risk. Type 2 diabetes is caused by both genetic and environmental factors. Scientists have linked several gene mutations to a higher diabetes risk. Not everyone who carries a mutation will get diabetes. But many people with diabetes do have one or more of these mutations. It can be difficult to separate genetic risk from environmental risk. The latter is often influenced by your family members. For example, parents with healthy eating habits are likely to pass them on to the next generation. On the other hand, genetics plays a big part in determining weight. Sometimes behaviors can’t take all the blame. Studies of twins suggest that type 2 diabetes might be linked to genetics. These studies were complicated by the environmental influences that also affect type 2 diabetes risk. To date, numerous mutations have been shown to affect type 2 diabetes risk. The contribution of each gene is generally small. However, each additional mutation you have seems to increase your Continue reading >>
Diabetes - Type 2 Diabetes
chromosome genetic t2dm insulin gene americans Type 2 diabetes is itself a group of disorders caused by some combination of insulin resistancewhich occurs when cells' ability to respond to insulin is compromisedand insulin deficiency, which occurs when the beta cells' ability to make insulin is compromised. T2DM has, in the past, been called adult-onset diabetes, because most people with T2DM were adults. It was also called non-insulin-dependent diabetes mellitus (NIDDM), because people with type 2 diabetes usually do not require insulin injections. In the Unites States, T2DM is especially prevalent among certain ethnic minorities, including African Americans, Mexican Americans, Asian Americans, and Native Americans. Obesity is a potent risk factor for T2DM. In the last thirty years, due to increased caloric intake and physical inactivity, both of which contribute to obesity, there was an explosion in the prevalence of T2DM, and it started occurring at younger ageseven in children. In addition to its association with an unhealthy lifestyle, T2DM is known to have a strong genetic component. Scientists have been searching throughout the genome for T2DM-susceptibility genes. One such gene, calpain 10 protease, was identified on chromosome 2. A common variant of this gene may predispose certain individuals to T2DM; however, the true significance of this gene variant remains to be determined. In addition, several candidate genes have shown some evidence of being involved in T2DM. However, the effect of any single candidate gene variant on the risk of developing T2DM is modest. A candidate gene is a gene for which prior knowledge of its function leads researchers to assess whether chemical variation in it is associated with a disease. As of 2002 there was no clinically avail Continue reading >>
Defining The Genetic Contribution Of Type 2 Diabetes Mellitus
Diabetes mellitus (DM) affects over 150 million people world wide, with a prevalence that varies markedly from population to population.1 Estimates predict that almost 300 million people will suffer from DM by 2025 (fig 1) with the vast majority being cases of diabetes mellitus type 2. Many risk factors have been identified which influence the prevalence (total number of cases as a percentage of the total population) or incidence (total number of new cases per year as a percentage of the total population). Factors of particular importance are a family history of diabetes mellitus, age, overweight, increased abdominal fat, hypertension, lack of physical exercise, and ethnic background. Several biochemical markers have also been identified as risk factors, including fasting hyperinsulinaemia, increased fasting proinsulin, and decreased HDL cholesterol.2 Both diabetes mellitus types 1 and 2 show a familial predisposition, which is a strong indication for the involvement of genes in people's susceptibility to the disease. However, the aetiology underlying types 1 and 2 is different and different genes are likely to be involved in each type of diabetes mellitus. The following discussion focuses on a genetic dissection of type 2 diabetes mellitus. The two most common forms of diabetes mellitus, type 1 and type 2, are both characterised by raised plasma glucose levels. Normal glucose homeostasis depends on the balance between glucose production by the liver and kidneys and glucose uptake by the brain, kidneys, muscles, and adipose tissue. Insulin, the predominant anabolic hormone involved, increases the uptake of glucose from the blood, enhances its conversion to glycogen and triglyceride, and also increases glucose oxidation. Plasma glucose levels are normally kept within a s Continue reading >>
The Genetic Basis Of Type 2 Diabetes
We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Type 2 Diabetes results from a complex physiologic process that includes the pancreatic beta cells, peripheral glucose uptake in muscle, the secretion of multiple cytokines and hormone-like molecules from adipocytes, hepatic glucose production, and likely the central nervous system. Consistent with the complex web of physiologic defects, the emerging picture of the genetics will involve a large number of risk susceptibility genes, each individually with relatively small effect (odds ratios below 1.2 in most cases). The challenge for the future will include cataloging and confirming the genetic risk factors, and understanding how these risk factors interact with each other and with the known environmental and lifestyle risk factors that increase the propensity to type 2 diabetes. Type 2 Diabetes Mellitus (T2DM) is a complex heterogeneous group of metabolic condition characterized by elevated levels of serum glucose, caused mainly by impairment in both insulin action and insulin secretion. T2DM exerts a huge toll in human suffering and economy. A recent evaluation using a computerized generic formal disease model (DisMod II) revealed that excess global mortality due to diabetes in the year 2000 was equivalent to 5.2% of all deaths and diabetes is likely to be the fifth leading cause of death, similar in magnitude to numbers reported for HIV/AIDS ( 1 ). The prevalence of diabetes for Continue reading >>
Gene Responsible For The Most Common Form Of Diabetes
International research teams studying two distinct populations have found variants in a gene that may predispose people to type 2 diabetes, the most common form of the disease. The researchers, who collaborated extensively in their work, report their findings in companion articles in the April issue of Diabetes. "This is an outstanding example of how scientists are using the tools of modern biology to understand the causes of our nation's most common - and most devastating - diseases," said Dr. Elias A. Zerhouni, director of the National Institutes of Health (NIH). "As researchers continue to build upon the foundation laid by the Human Genome Project, we can expect even swifter progress in our effort to understand, treat and eventually prevent many complex conditions such as diabetes, heart disease and mental illness." Homing in on a wide stretch of chromosome 20 - flagged by earlier studies as a likely location for a type 2 diabetes susceptibility gene - the teams identified four genetic variants, called single nucleotide polymorphisms (SNPs), which are strongly associated with type 2 diabetes in Finnish and Ashkenazi Jewish populations. All four SNPs cluster in the regulatory region of a single gene, hepatocyte nuclear factor 4 alpha (HNF4A), a transcription factor that acts as a "master switch" regulating the expression of hundreds of other genes. HNF4A turns genes on and off in many tissues, including the liver and pancreas. In the beta cells of the pancreas, it influences the secretion of insulin in response to glucose. "It's a nice coalescence of findings," said Dr. Francis S. Collins, director of the National Human Genome Research Institute (NHGRI) and senior author of the article describing the Finnish study results. "What we found is a common variation in this Continue reading >>
Genetics Of Type 2 Diabetes
Abstract BACKGROUND: Type 2 diabetes (T2D) is a complex disorder that is affected by multiple genetic and environmental factors. Extensive efforts have been made to identify the disease-affecting genes to better understand the disease pathogenesis, find new targets for clinical therapy, and allow prediction of disease. CONTENT: Our knowledge about the genes involved in disease pathogenesis has increased substantially in recent years, thanks to genomewide association studies and international collaborations joining efforts to collect the huge numbers of individuals needed to study complex diseases on a population level. We have summarized what we have learned so far about the genes that affect T2D risk and their functions. Although more than 40 loci associated with T2D or glycemic traits have been reported and reproduced, only a minor part of the genetic component of the disease has been explained, and the causative variants and affected genes are unknown for many of the loci. SUMMARY: Great advances have recently occurred in our understanding of the genetics of T2D, but much remains to be learned about the disease etiology. The genetics of T2D has so far been driven by technology, and we now hope that next-generation sequencing will provide important information on rare variants with stronger effects. Even when variants are known, however, great effort will be required to discover how they affect disease risk. Type 2 diabetes (T2D)2 is a common complex disorder with an increasing prevalence worldwide. In 2010 it was estimated that 6.6% of the world population of individuals 20–79 years old have diabetes, and that T2D constitutes approximately 90% of diabetes cases (1). This number is expected to increase epidemically as a consequence of an aging population and changes Continue reading >>
Scientists Find New Genetic Locations For Type 2 Diabetes
Scientists find new genetic locations for type 2 diabetes Scientists identify 111 new genetic locations that indicate susceptibility to type 2 diabetes. Scientists from University College London and Imperial College London in the United Kingdom have identified new genetic locations that might make some people more prone to developing type 2 diabetes. Type 2 diabetes affects hundreds of millions of people worldwide, and the numbers have skyrocketed in recent years. According to the World Health Organization (WHO), the number of people with diabetes has almost quadrupled in the past few decades, from 108 million in 1980 to 422 million in 2014. In the United States, 29 million people currently have diabetes, and 86 million are thought to have prediabetes. Until now, researchers were aware of 76 chromosomal locations , or "loci," that underlie this metabolic disease. However, new research analyzed the human genome further and found an additional 111. The new study - published in the American Journal of Human Genetics - was co-led by Dr. Nikolas Maniatis of University College London's (UCL) Genetics, Evolution, and Environment department, together with Dr. Toby Andrew of Imperial College London's Department of Genomics of Common Disease. Identifying the type 2 diabetes genetic loci Using a UCL-developed method of genetic mapping, Maniatis and team examined large samples of European and African American people, summarizing 5,800 cases of type 2 diabetes and almost 9,700 healthy controls. They found that the new loci - together with the ones previously identified - control the expression of more than 266 genes surrounding the genetic location of the disease. Most of the newly discovered loci were found outside of the coding regions of these genes, but within so-called hotspot Continue reading >>
Genetics Of Type 1 Diabetes
In western populations, each child has a 0.3–0.4% risk of developing diabetes by the age of 20 years; the risk increases 15-fold in siblings of an affected child. Lifetime risks are more difficult to estimate, but may be about twice as high as this. Some 50% of the genetic risk of type 1 diabetes is conferred by genes in the human leucocyte antigen (HLA) region on chromosome 6. The HLA Class II susceptibility haplotypes DR4-DQ8 and DR3-DQ2 are present in 90% of children with type 1 diabetes, whereas DR15-DQ6 is associated with protection. High risk HLA haplotypes in a child with no family history of disease confer a risk similar to that of having an affected sibling (5–6%), and this risk rises rapidly if one or both haplotypes are shared with the affected sibling. The promoter region of the insulin gene on chromosome 11 contributes about 10% of genetic susceptibility. Many other genes (currently more than 40) make a minor contribution to type 1 diabetes, and several are of particular interest because they influence different aspects of immune function. Their ability to predict diabetes is, however, limited. Empirical risks By the age of 20 years, type 1 diabetes will have affected some 0.3–0.4% of children in the background population in western countries, and about 6% of siblings of childhood onset cases, giving a ratio (λs) of 15. Early-onset diabetes carries a higher familial risk, and affected fathers are more likely to transmit type 1 diabetes to their offspring than affected mothers, with risks being 6–9% and 1–3%, respectively.[1] These estimates represent the risk of diabetes development by young adult life, not the lifetime risk. The latter is not well established, and may be as high as 1% in the background population and 15% in siblings. Siblings wh Continue reading >>
A Genomewide Search For Type 2 Diabetessusceptibility Genes In Indigenous Australians
Volume 70, Issue 2 , February 2002, Pages 349-357 A Genomewide Search for Type 2 DiabetesSusceptibility Genes in Indigenous Australians The prevalence of type 2 diabetes among Australian residents is 7.5%; however, prevalence rates up to six times higher have been reported for indigenous Australian communities. Epidemiological evidence implicates genetic factors in the susceptibility of indigenous Australians to type 2 diabetes and supports the hypothesis of the thrifty genotype, but, to date, the nature of the genetic predisposition is unknown. We have ascertained clinical details from a community of indigenous Australian descent in North Stradbroke Island, Queensland. In this population, the phenotype is characterized by severe insulin resistance. We have conducted a genomewide scan, at an average resolution of 10 cM, for type 2 diabetessusceptibility genes in a large multigeneration pedigree from this community. Parametric linkage analysis undertaken using FASTLINK version 4.1p yielded a maximum two-point LOD score of +2.97 at marker D2S2345. Multipoint analysis yielded a peak LOD score of +3.9 <1 cM from marker D2S2345, with an 18-cM 3-LOD support interval. Secondary peak LOD scores were noted on chromosome 3 (+1.8 at recombination fraction [] 0.05, at marker D3S1311) and chromosome 8 (+1.77 at =0.0, at marker D8S549). These chromosomal regions are likely to harbor novel susceptibility genes for type 2 diabetes in the indigenous Australian population. Continue reading >>
Susceptibility Locus For Early-onset Non-insulin Dependent (type 2) Diabetes Mellitus Maps To Chromosome 20q, Proximal To The Phosphoenolpyruvate Carboxykinase Gene | Human Molecular Genetics | Oxford Academic
Several candidate genes for non-insulin-dependent diabetes mellitus (NIDDM) map on chromosome 20, including the phosphoenolpyruvate carboxykinase gene (PCK1) and one of the maturity onset diabetes of the young genes (MODY1). Thus, we have investigated the entire long arm of chromosome 20. Linkage analyses were conducted in a total sample of 148 NIDDM families (301 NIDDM sib pairs) and in a subset of 42 early onset NIDDM families, where genetic components are likely to play a more important role (55 NIDDM sib pairs diagnosed at or before 45 years of age), using 10 highly polymorphic markers with an average map density of 7.5 cM. Using affected sib pair methods (two-point linkage and multipoint linkage analyses), significant results were obtained with the 20q13 region, in the vicinity of the PCK1 locus, only in the subset of 55 early onset NIDDM sib pairs (multipoint MLS = 2.74, P = 0.0004; MLS = 2.34, P = 0.0009 when using a conservative weighting procedure). Moreover, another region spanning the ribophorin II (RPNII), phospholipase C (PLC1) and adenosine deaminase (ADA) loci suggested linkage with NIDDM (multipoint MLS of 1.81 in all NIDDM sib pairs, P= 0.003; MLS = 1.31, P = 0.012 when using a conservative weighting procedure). Whereas our study suggests the location of a susceptibility locus for early onset NIDDM in the PCK1 gene region, further investigation in larger data sets is required to confirm these results and assess the role of other regions on chromosome 20q in human NIDDM. It is widely accepted that non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous metabolic disorder with a complex pattern of inheritance. NIDDM exhibits a combination of two major alterations, insulin resistance and pancreatic -cell dysfunction, but the primary defect is s Continue reading >>
- Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System for the Management of Adults With Diabetes | Journal of the Endocrine Society | Oxford Academic
- DNA methylation links genetics, fetal environment, and an unhealthy lifestyle to the development of type 2 diabetes
- Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes
Type 2 Diabetes: Evidence For Linkage On Chromosome 20 In 716 Finnish Affected Sib Pairs
Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs Soumitra Ghosh ,* Richard M. Watanabe , Elizabeth R. Hauser , Timo Valle , Victoria L. Magnuson ,* Michael R. Erdos ,* Carl D. Langefeld , James Balow, Jr. ,* Delphine S. Ally ,* Kimmo Kohtamaki , Peter Chines ,* Gunther Birznieks ,* Hong-Shi Kaleta , Anjene Musick ,* Catherine Te ,* Joyce Tannenbaum ,* William Eldridge ,* Shane Shapiro ,* Colin Martin ,* Alyson Witt ,* Alistair So ,* Jennie Chang ,* Ben Shurtleff ,* Rachel Porter ,* Kristina Kudelko ,* Arun Unni ,* Leonid Segal ,* Ravi Sharaf ,* Jillian Blaschak-Harvan , Johan Eriksson , Tuula Tenkula , Gabriele Vidgren , Christian Ehnholm , Eva Tuomilehto-Wolf , William Hagopian , Thomas A. Buchanan ,** Jaakko Tuomilehto , Richard N. Bergman , Francis S. Collins ,* and Michael Boehnke *Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029; Section of Medical Genetics, Department of Medicine, Duke University Medical Center, Durham, NC 27710; Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; Department of Medicine, University of Washington, Seattle, WA 98195-5840; **Department of Medicine, University of Southern California, Los Angeles, CA 90089-2538; Department of Physiology and Biophysics, School of Medicine, University of Southern California, Los Angeles, CA 90089-2538 *Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Department of Biostatistics, School of Public Health, Universi Continue reading >>
Type 2 Diabetes Genetic Mapping Identifies New 'loci'
Follow all of ScienceDaily's latest research news and top science headlines ! Type 2 diabetes genetic mapping identifies new 'loci' Scientists are closer to understanding the genetic causes of type 2 diabetes by identifying 111 new chromosome locations ('loci') on the human genome that indicate susceptibility to the disease, according to a new study. Scientists are closer to understanding the genetic causes of type 2 diabetes by identifying 111 new chromosome locations ('loci') on the human genome that indicate susceptibility to the disease, according to a UCL-led study in collaboration with Imperial College London. Type 2 diabetes is the world's most widespread and devastating metabolic disorder and previously only 76 loci were known and studied. Very few these loci are found in the African American population where the prevalence of type 2 diabetes is almost twice that in the European American population (19% vs. 10%). Of the additional 111 loci identified by the team, 93 (84%) are found in both African American and European populations and only 18 are European-specific. The study, published today in the American Journal of Human Genetics, used a method developed at UCL based on highly informative genetic maps to investigate complex disorders such as type 2 diabetes. European and African American sample populations comprising 5,800 type 2 diabetes case subjects and 9,691 control subjects were analysed, revealing multiple type 2 diabetes loci at regulatory hotspots across the genome. "No disease with a genetic predisposition has been more intensely investigated than type 2 diabetes. We've proven the benefits of gene mapping to identify hundreds of locations where causal mutations might be across many populations, including African Americans. This provides a larger num Continue reading >>
- Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes
- Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes
- Genetic Screening for the Risk of Type 2 Diabetes
Omim Entry - # 125853 - Diabetes Mellitus, Noninsulin-dependent; Niddm
A number sign (#) is used with this entry because of evidence that more than one gene is involved in the causation of noninsulin-dependent diabetes mellitus (NIDDM). See 601283 for description of a form of NIDDM linked to 2q, which may be caused by mutation in the gene encoding calpain-10 (CAPN10; 605286 ). See 601407 for description of a chromosome 12q locus, NIDDM2, found in a Finnish population. See 603694 for description of a locus on chromosome 20, NIDDM3. See 608036 for description of a locus on chromosome 5q34-q35, NIDDM4. See 616087 for description of NIDDM5, which comprises susceptibility related to a nonsense mutation in the TBC1D4 gene ( 612465 ) on chromosome 13q22. A mutation has been observed in hepatocyte nuclear factor-4-alpha (HNF4A; 600281.0004 ) in a French family with NIDDM of late onset. Mutations in the NEUROD1 gene ( 601724 ) on chromosome 2q32 were found to cause type II diabetes mellitus in 2 families. Mutation in the GLUT2 glucose transporter was associated with NIDDM in 1 patient ( 138160.0001 ). Mutation in the MAPK8IP1 gene, which encodes the islet-brain-1 protein, was found in a family with type II diabetes in individuals in 4 successive generations ( 604641.0001 ). Polymorphism in the KCNJ11 gene ( 600937.0014 ) confers susceptibility. In French white families, Vionnet et al. (2000) found evidence for a susceptibility locus for type II diabetes on 3q27-qter. They confirmed the diabetes susceptibility locus on 1q21-q24 reported by Elbein et al. (1999) in whites and by Hanson et al. (1998) in Pima Indians. A mutation in the GPD2 gene ( 138430.0001 ) on chromosome 2q24.1, encoding mitochondrial glycerophosphate dehydrogenase, was found in a patient with type II diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX Continue reading >>
Type 2 Diabetes On Chromosome 20q13.1q13.2
We previously reported suggestive linkage between type 2 diabetes and markers in a region on chromosome 20q using data from a collection of 29 Caucasian families in which type 2 diabetes with middle-ageonset was segregated as an autosomal-dominant disorder. To map more precisely the susceptibility locus (or loci) within this broad region, we increased the family collection and genotyped all families for additional markers, both within the critical region and spaced over the rest of chromosome 20. Altogether 526 individuals (including 241 with diabetes) from the total collection of 43 families were included in the study. All individuals were genotyped for 23 highly polymorphic markers. Positive evidence for linkage was found for a 10-cM region on the long arm of chromosome 20q13.1q13.2 between markers D20S119 and D20S428. The strongest evidence in two-point as well as multipoint linkage analysis (P = 1.8 X105) occurred at the position corresponding to marker D20S196. The individuals with diabetes in the seven most strongly linked families had high serum insulin levels during fasting and 2-h postglucose load periods. We did not find any evidence for linkage between type 2 diabetes and any other region on chromosome 20. In conclusion, our larger and more comprehensive study showed very strong evidence for a susceptibility gene for insulin-resistant type 2 diabetes located on the long arm of chromosome 20 around marker D20S196. The development of type 2 diabetes is strongly influenced by genetic factors [ 1 , 2 ]. Recently, genes responsible for several rare forms of autosomal-dominant early-onset type 2 diabetes, also known as maturity-onset diabetes of the young (MODY), have been identified [ 3 , 4 ]. Although mutations in these genes are infrequent, their identification Continue reading >>
