Phenome-wide Association Study
In genetics and genetic epidemiology, a phenome-wide association study, abbreviated PheWAS, is a study design in which the association between single-nucleotide polymorphisms or other types of DNA variants is tested across a large number of different phenotypes. The aim of PheWAS studies (or PheWASs) is to examine the causal linkage between known sequence differences and any type of trait, including molecular, biochemical, cellular, and especially clinical diagnoses and outcomes. It is a complementary approach to the genome-wide association study, or GWAS, methodology. A fundamental difference between GWAS and PheWAS designs is the direction of inference: in a PheWAS it is from exposure (the DNA variant) to many possible outcomes, that is, from SNPs to differences in phenotypes and disease risk. In a GWAS, the polarity of analysis is from one or a few phenotypes to many possible DNA variants. The approach has proven useful in rediscovering previously reported genotype-phenotype ass ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Genetic Epidemiology
Genetic epidemiology is the study of the role of genetic factors in determining health and disease in families and in populations, and the interplay of such genetic factors with environmental factors. Genetic epidemiology seeks to derive a statistical and quantitative analysis of how genetics work in large groups. Definition The use of the term ''Genetic epidemiology'' emerged in the mid-1980s as a new scientific field. In formal language, genetic epidemiology was defined by Newton Morton, one of the pioneers of the field, as "a science which deals with the etiology, distribution, and control of disease in groups of relatives and with inherited causes of disease in populations". It is closely allied to both molecular epidemiology and statistical genetics, but these overlapping fields each have distinct emphases, societies and journals. One definition of the field closely follows that of behavior genetics, defining genetic epidemiology as "the scientific discipline that deals ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Bonferroni Correction
In statistics, the Bonferroni correction is a method to counteract the multiple comparisons problem. Background The method is named for its use of the Bonferroni inequalities. An extension of the method to confidence intervals was proposed by Olive Jean Dunn. Statistical hypothesis testing is based on rejecting the null hypothesis if the likelihood of the observed data under the null hypotheses is low. If multiple hypotheses are tested, the probability of observing a rare event increases, and therefore, the likelihood of incorrectly rejecting a null hypothesis (i.e., making a Type I error) increases. The Bonferroni correction compensates for that increase by testing each individual hypothesis at a significance level of \alpha/m, where \alpha is the desired overall alpha level and m is the number of hypotheses. For example, if a trial is testing m = 20 hypotheses with a desired \alpha = 0.05, then the Bonferroni correction would test each individual hypothesis at \alpha = 0.05/20 = ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Thiopurine Methyltransferase
Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the ''TPMT'' gene. A pseudogene for this locus is located on chromosome 18q. Function Thiopurine methyltransferase methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine. This enzyme metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Clinical significance Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents and immunosuppressive drugs. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals. About 1/300 individual is deficient for the enzyme. Pharmacology TPMT is best known for its role in the metabolism of the thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. TPMT ca ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas ulcerative colitis primarily affects the colon and the rectum. IBD also occurs in dogs and is thought to arise from a combination of host genetics, intestinal microenvironment, environmental components and the immune system. There is an ongoing discussion, however, that the term "chronic enteropathy" might be better to use than "inflammatory bowel disease" in dogs because it differs from IBD in humans in how the dogs respond to treatment. For example, many dogs respond to only dietary changes compared to humans with IBD, who often need immunosuppressive treatment. Some dogs may also need immunosuppressant or antibiotic treatment when dietary changes are not enough. After having excl ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Thiopurine
The thiopurine drugs are purine antimetabolites widely used in the treatment of acute lymphoblastic leukemia, autoimmune disorders (e.g., Crohn's disease, rheumatoid arthritis), and organ transplant recipients. Metabolism is catalyzed by S-methyltransferase. Litigation over patents covering diagnostic kits to monitor the dosing of these drugs led to a US Supreme Court case, ''Mayo Collaborative Services v. Prometheus Laboratories, Inc.'' that dramatically changed the nature of patent law in the United States.Supreme Court Decision. Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150, Slip Op. at 16Decision/ref>Gene Quinn''Killing Industry: The Supreme Court Blows Mayo v. Prometheus'' (March 20, 2012). See also * 6-Mercaptopurine (6-MP) * 6-Thioguanine (6-TG) * Azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Type 2 Diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes. In ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Hyperinsulinemia
Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions, as well as non-nutritive sugars in the diet. While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease. Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulinism, including nesidioblastosis. Hyperinsulinemia is associated with hypertension, obesity, dyslipidemia, insulin resistance, and glucose intolerance. These conditions are collectively known as metabolic syndrome. This close association between h ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Linear Regression
In statistics, linear regression is a linear approach for modelling the relationship between a scalar response and one or more explanatory variables (also known as dependent and independent variables). The case of one explanatory variable is called '' simple linear regression''; for more than one, the process is called multiple linear regression. This term is distinct from multivariate linear regression, where multiple correlated dependent variables are predicted, rather than a single scalar variable. In linear regression, the relationships are modeled using linear predictor functions whose unknown model parameters are estimated from the data. Such models are called linear models. Most commonly, the conditional mean of the response given the values of the explanatory variables (or predictors) is assumed to be an affine function of those values; less commonly, the conditional median or some other quantile is used. Like all forms of regression analysis, linear regressio ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Logistic Regression
In statistics, the logistic model (or logit model) is a statistical model that models the probability of an event taking place by having the log-odds for the event be a linear function (calculus), linear combination of one or more independent variables. In regression analysis, logistic regression (or logit regression) is estimation theory, estimating the parameters of a logistic model (the coefficients in the linear combination). Formally, in binary logistic regression there is a single binary variable, binary dependent variable, coded by an indicator variable, where the two values are labeled "0" and "1", while the independent variables can each be a binary variable (two classes, coded by an indicator variable) or a continuous variable (any real value). The corresponding probability of the value labeled "1" can vary between 0 (certainly the value "0") and 1 (certainly the value "1"), hence the labeling; the function that converts log-odds to probability is the logistic function, h ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Pleiotropy
Pleiotropy (from Greek , 'more', and , 'way') occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function. Pleiotropy can arise from several distinct but potentially overlapping mechanisms, such as gene pleiotropy, developmental pleiotropy, and selectional pleiotropy. Gene pleiotropy occurs when a gene product interacts with multiple other proteins or catalyzes multiple reactions. Developmental pleiotropy occurs when mutations have multiple effects on the resulting phenotype. Selectional pleiotropy occurs when the resulting phenotype has many effects on fitness (depending on factors such as age and gender). An example of pleiotropy is phenylketonuria, an inherited ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Multiple Sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, blindness in one eye, muscle weakness, and trouble with sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. While the cause is unclear, the underlying mechanism is thought to be either destruction by the immune s ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with hemoptysis, blood-containing sputum, mucus, fever, night sweats, and weight loss. It was historically referred to as consumption due to the weight loss associated with the disease. Infection of other organs can cause a wide range of symptoms. Tuberculosis is Human-to-human transmission, spread from one person to the next Airborne disease, through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. People with Latent TB do not spread the disease. Active infection occurs more often in people wi ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |