Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Genetic Variation: Genotypic differences observed among individuals in a population.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Genetics, Population: The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES.Genetic Loci: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.Models, Statistical: Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.Genetic Processes: Those biological processes that are involved in the transmission of hereditary traits from one organism to another.European Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Europe.Meta-Analysis as Topic: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Sample Size: The number of units (persons, animals, patients, specified circumstances, etc.) in a population to be studied. The sample size should be big enough to have a high likelihood of detecting a true difference between two groups. (From Wassertheil-Smoller, Biostatistics and Epidemiology, 1990, p95)Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Genetic Heterogeneity: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)Epistasis, Genetic: A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.Quantitative Trait, Heritable: A characteristic showing quantitative inheritance such as SKIN PIGMENTATION in humans. (From A Dictionary of Genetics, 4th ed)Quantitative Trait Loci: Genetic loci associated with a QUANTITATIVE TRAIT.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Data Interpretation, Statistical: Application of statistical procedures to analyze specific observed or assumed facts from a particular study.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Gene-Environment Interaction: The combined effects of genotypes and environmental factors together on phenotypic characteristics.Bayes Theorem: A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result.Genotyping Techniques: Methods used to determine individuals' specific ALLELES or SNPS (single nucleotide polymorphisms).Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Pharmacogenetics: A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.Principal Component Analysis: Mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Disease: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.Genetics, Medical: A subdiscipline of human genetics which entails the reliable prediction of certain human disorders as a function of the lineage and/or genetic makeup of an individual or of any two parents or potential parents.Genetic Research: Research into the cause, transmission, amelioration, elimination, or enhancement of inherited disorders and traits.Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters.Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly.Statistical Distributions: The complete summaries of the frequencies of the values or categories of a measurement made on a group of items, a population, or other collection of data. The distribution tells either how many or what proportion of the group was found to have each value (or each range of values) out of all the possible values that the quantitative measure can have.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.Family: A social group consisting of parents or parent substitutes and children.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Epidemiologic Research Design: The form and structure of analytic studies in epidemiologic and clinical research.Growth Differentiation Factor 5: A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics.Homozygote: An individual in which both alleles at a given locus are identical.Serotonin Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.Apolipoprotein E2: One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.Multifactorial Inheritance: A phenotypic outcome (physical characteristic or disease predisposition) that is determined by more than one gene. Polygenic refers to those determined by many genes, while oligogenic refers to those determined by a few genes.African Americans: Persons living in the United States having origins in any of the black groups of Africa.Risk: The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships.Bias (Epidemiology): Any deviation of results or inferences from the truth, or processes leading to such deviation. Bias can result from several sources: one-sided or systematic variations in measurement from the true value (systematic error); flaws in study design; deviation of inferences, interpretations, or analyses based on flawed data or data collection; etc. There is no sense of prejudice or subjectivity implied in the assessment of bias under these conditions.Catechol O-Methyltransferase: Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.Molecular Epidemiology: The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.Publication Bias: The influence of study results on the chances of publication and the tendency of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Publication bias has an impact on the interpretation of clinical trials and meta-analyses. Bias can be minimized by insistence by editors on high-quality research, thorough literature reviews, acknowledgement of conflicts of interest, modification of peer review practices, etc.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Monte Carlo Method: In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993)African Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Africa.Chromosomes, Human, Pair 6: A specific pair GROUP C CHROMSOMES of the human chromosome classification.China: A country spanning from central Asia to the Pacific Ocean.HapMap Project: A coordinated international effort to identify and catalog patterns of linked variations (HAPLOTYPES) found in the human genome across the entire human population.Confounding Factors (Epidemiology): Factors that can cause or prevent the outcome of interest, are not intermediate variables, and are not associated with the factor(s) under investigation. They give rise to situations in which the effects of two processes are not separated, or the contribution of causal factors cannot be separated, or the measure of the effect of exposure or risk is distorted because of its association with other factors influencing the outcome of the study.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression.Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Population Groups: Individuals classified according to their sex, racial origin, religion, common place of living, financial or social status, or some other cultural or behavioral attribute. (UMLS, 2003)Environment: The external elements and conditions which surround, influence, and affect the life and development of an organism or population.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Nerve Tissue ProteinsInternet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Probability: The study of chance processes or the relative frequency characterizing a chance process.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Asthma: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.Risk Assessment: The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)Chromosomes, Human, Pair 4: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.Smoking: Inhaling and exhaling the smoke of burning TOBACCO.Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.Twin Studies as Topic: Methods of detecting genetic etiology in human traits. The basic premise of twin studies is that monozygotic twins, being formed by the division of a single fertilized ovum, carry identical genes, while dizygotic twins, being formed by the fertilization of two ova by two different spermatozoa, are genetically no more similar than two siblings born after separate pregnancies. (Last, J.M., A Dictionary of Epidemiology, 2d ed)Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Chromosomes, Human, Pair 9: A specific pair of GROUP C CHROMSOMES of the human chromosome classification.Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Inheritance Patterns: The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Multifactor Dimensionality Reduction: A statistical tool for detecting and modeling gene-gene interactions. It is a non-parametric and model-free approach.Chromosomes, Human, Pair 10: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Siblings: Persons or animals having at least one parent in common. (American College Dictionary, 3d ed)Chromosomes, Human, Pair 1: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Chromosomes, Human, Pair 2: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.Chromosomes, Human, Pair 8: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Macular Degeneration: Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.Chromosomes, Human, Pair 5: One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).Chromosomes, Human, Pair 15: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Crohn Disease: A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.Penetrance: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Biostatistics: The application of STATISTICS to biological systems and organisms involving the retrieval or collection, analysis, reduction, and interpretation of qualitative and quantitative data.EuropeDiseases in Twins: Disorders affecting TWINS, one or both, at any age.Exfoliation Syndrome: The deposition of flaky, translucent fibrillar material most conspicuous on the anterior lens capsule and pupillary margin but also in both surfaces of the iris, the zonules, trabecular meshwork, ciliary body, corneal endothelium, and orbital blood vessels. It sometimes forms a membrane on the anterior iris surface. Exfoliation refers to the shedding of pigment by the iris. (Newell, Ophthalmology, 7th ed, p380)HLA-DRB1 Chains: A subtype of HLA-DRB beta chains that includes over one hundred allele variants. The HLA-DRB1 subtype is associated with several of the HLA-DR SEROLOGICAL SUBTYPES.Longevity: The normal length of time of an organism's life.Tobacco Use Disorder: Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included.Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.Chromosomes, Human, Pair 11: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.DNA Copy Number Variations: Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.JapanDiabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.Chromosomes, Human, Pair 3: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.HLA-DQ beta-Chains: Transmembrane proteins that form the beta subunits of the HLA-DQ antigens.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.Nuclear Family: A family composed of spouses and their children.False Positive Reactions: Positive test results in subjects who do not possess the attribute for which the test is conducted. The labeling of healthy persons as diseased when screening in the detection of disease. (Last, A Dictionary of Epidemiology, 2d ed)Continental Population Groups: Groups of individuals whose putative ancestry is from native continental populations based on similarities in physical appearance.Multiple Sclerosis: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Chi-Square Distribution: A distribution in which a variable is distributed like the sum of the squares of any given independent random variable, each of which has a normal distribution with mean of zero and variance of one. The chi-square test is a statistical test based on comparison of a test statistic to a chi-square distribution. The oldest of these tests are used to detect whether two or more population distributions differ from one another.Heredity: The transmission of traits encoded in GENES from parent to offspring.Chromosomes, Human, Pair 12: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Gene Regulatory Networks: Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Apolipoprotein C-I: A 6.6-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS; INTERMEDIATE-DENSITY LIPOPROTEINS; and HIGH-DENSITY LIPOPROTEINS. Apo C-I displaces APO E from lipoproteins, modulate their binding to receptors (RECEPTORS, LDL), and thereby decrease their clearance from plasma. Elevated Apo C-I levels are associated with HYPERLIPOPROTEINEMIA and ATHEROSCLEROSIS.Chromosomes, Human: Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.Data Mining: Use of sophisticated analysis tools to sort through, organize, examine, and combine large sets of information.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Biometry: The use of statistical and mathematical methods to analyze biological observations and phenomena.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Chromosomes, Human, X: The human female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in humans.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Receptors, Dopamine D4: A subtype of dopamine D2 receptors that has high affinity for the antipsychotic CLOZAPINE.Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."GermanyGenetic Pleiotropy: A phenomenon in which multiple and diverse phenotypic outcomes are influenced by a single gene (or single gene product.)Quality Control: A system for verifying and maintaining a desired level of quality in a product or process by careful planning, use of proper equipment, continued inspection, and corrective action as required. (Random House Unabridged Dictionary, 2d ed)Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Protein Tyrosine Phosphatase, Non-Receptor Type 22: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an N-terminal catalytic domain and a C-terminal PROLINE-rich domain. The phosphatase subtype is predominantly expressed in LYMPHOCYTES and plays a key role in the inhibition of downstream T-LYMPHOCYTE activation. Polymorphisms in the gene that encodes this phosphatase subtype are associated with a variety of AUTOIMMUNE DISEASES.Body Mass Index: An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)Computer Graphics: The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation.Alcoholism: A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)Mathematical Computing: Computer-assisted interpretation and analysis of various mathematical functions related to a particular problem.Apolipoprotein E4: A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.FinlandMajor Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.Gene Dosage: The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.Markov Chains: A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system.Aryldialkylphosphatase: An enzyme which catalyzes the hydrolysis of an aryl-dialkyl phosphate to form dialkyl phosphate and an aryl alcohol. It can hydrolyze a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. It may also mediate an enzymatic protection of LOW DENSITY LIPOPROTEINS against oxidative modification and the consequent series of events leading to ATHEROMA formation. The enzyme was previously regarded to be identical with Arylesterase (EC 3.1.1.2).Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.HLA-C Antigens: Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).United StatesReceptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Korea: Former kingdom, located on Korea Peninsula between Sea of Japan and Yellow Sea on east coast of Asia. In 1948, the kingdom ceased and two independent countries were formed, divided by the 38th parallel.Breast Neoplasms: Tumors or cancer of the human BREAST.Sex Factors: Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances.Hispanic Americans: Persons living in the United States of Mexican (MEXICAN AMERICANS), Puerto Rican, Cuban, Central or South American, or other Spanish culture or origin. The concept does not include Brazilian Americans or Portuguese Americans.Clusterin: A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.Statistics as Topic: The science and art of collecting, summarizing, and analyzing data that are subject to random variation. The term is also applied to the data themselves and to the summarization of the data.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Attention Deficit Disorder with Hyperactivity: A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V)HLA-B Antigens: Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.Epidemiologic Methods: Research techniques that focus on study designs and data gathering methods in human and animal populations.Receptors, Calcitriol: Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors.Methylenetetrahydrofolate Reductase (NADPH2): A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Inflammatory Bowel Diseases: Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMexican Americans: Persons living in the United States of Mexican descent.

Genotype-phenotype analyses of classic neuronal ceroid lipofuscinosis (NCLs): genetic predictions from clinical and pathological findings. (1/3604)

OBJECTIVE: Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). METHODS: Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. RESULTS: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases. CONCLUSION: Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.  (+info)

The genotype and phenotype studies of 40 Chinese patients with X-linked adrenoleukodystrophy (X-ALD). (2/3604)

OBJECTIVE: To elucidate the phenotype and the genotype-phenotype correlations in Chinese patients with X-linked adrenoleukodystrophy (X-ALD). METHODS: Clinical features of 40 Chinese patients with X-ALD were studied and mutation spectrums were investigated by polymerase chain reaction (PCR) and sequencing. RESULTS: Among these patients, four were siblings from two unrelated families, the others were unrelated. There were 31 cases with childhood cerebral (CCALD), 8 cases with adolescent cerebral (ACALD) and 1 case with adrenomyeloneuropathy (AMN). Visual impairment, which presented in 12 cases (30%), was the most common initial symptom. Nine (69%) of 13 cases who had hydrocortisone and ACTH measured showed adrenal insufficiency. By follow-up date, 19 cases (47.5%) were dead. The interval from onset to death varied from 1 to 6 years and the average were 3.3 years. The mean age at death was 10.5 years. Eleven cases (27.5%) were in vegetable state. The mean interval from onset to apparently vegetable state was 2.8 years (range from 1 to 6 years). Four cases had progressive neurological disability. Four cases were lost follow-up. One case with CCALD and one case with ACALD progressed slowly. The courses of the disease of these two patients were 5 years and 15 years respectively. Thirty five mutations were identified in 40 cases. Most were located within exon 1-3 (40%, 16/40) and exon 6-8 (42%, 17/40). There is a distinct clustering of missense mutations in exon 6 (17%, 7/40). Five types of mutations were associated with CCALD, three with ACALD and a missense mutation was identified in the patients with AMN. The two patients with long disease courses had a missense mutation c.1559 T>A and a nonsense mutation c.1785 G>A respectively. The siblings with similar manifestations and onset age were observed in two families, whose mutations were c.887 A>G and c.1028 G>T. CONCLUSION: The phenotypes, disease severity and rate of neurodegeneration could not be predicted by the nature of mutations.  (+info)

Leveraging hierarchical population structure in discrete association studies. (3/3604)

Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in Arabidopsis thaliana. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding. Analysis tools based on these models are available on the internet as both web based applications and downloadable source code at http://atom.research.microsoft.com/bio/phylod.aspx.  (+info)

Large-scale in silico mapping of complex quantitative traits in inbred mice. (4/3604)

Understanding the genetic basis of common disease and disease-related quantitative traits will aid in the development of diagnostics and therapeutics. The processs of gene discovery can be sped up by rapid and effective integration of well-defined mouse genome and phenome data resources. We describe here an in silico gene-discovery strategy through genome-wide association (GWA) scans in inbred mice with a wide range of genetic variation. We identified 937 quantitative trait loci (QTLs) from a survey of 173 mouse phenotypes, which include models of human disease (atherosclerosis, cardiovascular disease, cancer and obesity) as well as behavioral, hematological, immunological, metabolic, and neurological traits. 67% of QTLs were refined into genomic regions <0.5 Mb with approximately 40-fold increase in mapping precision as compared with classical linkage analysis. This makes for more efficient identification of the genes that underlie disease. We have identified two QTL genes, Adam12 and Cdh2, as causal genetic variants for atherogenic diet-induced obesity. Our findings demonstrate that GWA analysis in mice has the potential to resolve multiple tightly linked QTLs and achieve single-gene resolution. These high-resolution QTL data can serve as a primary resource for positional cloning and gene identification in the research community.  (+info)

Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol. (5/3604)

The identification of DNA sequence variants underlying human complex phenotypes remains a significant challenge for several reasons: individual variants can have small phenotypic effects or low population frequencies, and multiple allelic variants may act in concert to affect a trait. We evaluated the combined effect of allelic variants in seven genes involved in high-density lipoprotein (HDL) metabolism, using forward stepwise regression. Analysis of all known common single-nucleotide polymorphisms (SNPs) in the seven candidate genes revealed four variants that were associated with incremental changes in HDL cholesterol levels in three independent samples. Conversely, analysis of 660 polymorphisms in eight genes that do not appear to be involved in HDL metabolism did not identify any associations with plasma HDL-cholesterol levels. These data indicate that several common SNPs act in concert to influence plasma levels of HDL cholesterol.  (+info)

ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention. (6/3604)

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Supporting family adaptation to presymptomatic and "untreatable" conditions in an era of expanded newborn screening. (7/3604)

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Differential effects of COMT on gait and executive control in aging. (8/3604)

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  • Given the number of potentially identifiable genetic markers and the multitude of clinical outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epidemiology is a task of unprecedented scale. (scienceopen.com)
  • The combination of vertebral defects, anal atresia, cardiac anomalies, tracheo-esophageal fistula, radial dysplasia and limb anomalies, and renal anomalies, termed VACTERL association, has been used as a clinical descriptor for a specific group of phenotypic manifestations that have been observed to occur together. (clinicaltrials.gov)
  • The purpose of the present study is to increase the understanding of the clinical manifestations and genetic causes of VACTERL association through detailed physical, laboratory, and radiological studies. (clinicaltrials.gov)
  • We also plan to examine the spectrum of clinical characteristics in VACTERL association to facilitate early diagnosis and clinical management, including genetic counseling. (clinicaltrials.gov)
  • We also make suggestions about the design of genetic association studies in ischaemic stroke with regard to stroke subtype classification, candidate pathways, subgroups, intermediate phenotypes and potential clinical impact. (nih.gov)
  • Elucidating the underlying genetic variations influencing various complex diseases is one of the major challenges currently facing clinical genetic research. (hindawi.com)
  • Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. (pnas.org)
  • Clinical studies showed that enlargement of the vestibular aqueduct was the most common structural abnormality associated with EVA, rather than a malformed cochlea, and in some people it was the only structure that was abnormal. (vestibular.org)
  • We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. (uni-muenchen.de)
  • We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. (uni-muenchen.de)
  • The clinical interpretation and implementation of genetic association studies with respect to disease risk and treatment is not yet well defined and remains an important area of future research. (diva-portal.org)
  • Both clinical and pharmacologic studies have implicated the role of brain-derived neurotrophic factor (BDNF) as a susceptibility locus for the development of mental illness, including depression, bipolar disorder, and schizophrenia. (soton.ac.uk)
  • Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields. (omicsonline.org)
  • Clinical data of patients consisting of binary/dichotomous representation of symptoms and their calculated severity scores were also available from this study. (springer.com)
  • Although a genetic predisposition may exist, the importance of this-and thus the clinical significance-is unclear," the authors write. (ptproductsonline.com)
  • We performed a GWA study on serum 25-hydroxyvitamin D (25(OH)D) and response to supplementation in 761 healthy term-born Finnish 24-month-old children, who participated in a randomized clinical trial comparing effects of 10 mug and 30 mug of daily vitamin D supplementation from age 2 weeks to 24 months. (galileo-training.com)
  • However, besides evaluating the overall statistical significance, the clinical relevance of a genetic association depends on the magnitude of risk conferred to the carriers of allele mt [ 3 ]. (biomedcentral.com)
  • Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. (nottingham.ac.uk)
  • Power for genetic association studies with random allele frequencies and genotype distributions. (springer.com)
  • In this analysis we included 3,548 participants from British Women's Heart and Health Study (BWHHS) and 6,836 mothers from Avon Longitudinal Study of Parents and Children (ALSPAC) who had complete data on genotype and depression outcomes. (soton.ac.uk)
  • The study suggests that VKORC1 genotype is the primary genetic determinant of variability in warfarin dose requirements in African Americans. (acc.org)
  • We analyzed genotype probabilities of ≈8.6 million variants, imputed to the Genome of the Netherlands project reference panel, with a minor allele frequency ≥1% for an association with recurrent VT. (ovid.com)
  • They then compared the genotype and minor allele frequencies of all the single-nucleotide variants in athletes with no ACL injuries (n=732) to athletes with ACL injury before or after inclusion in the study (n=119). (ptproductsonline.com)
  • Thus, in view of a significant association, the following contrasts of genotypes are defined by merging information of the genotype distribution [ 4 ], and estimated with the odds ratio (OR) and its 95% confidence interval (CI): (i) the additive contrast, which is defined as the comparison between the extreme genotypes - mtmt vs. wtwt - (in this contrast the heterozygotes are ignored. (biomedcentral.com)
  • Studies of genetic association aim to test whether single-locus alleles or genotype frequencies (or more generally, multilocus haplotype frequencies) differ between two groups of individuals (usually diseased subjects and healthy controls). (wikipedia.org)
  • A difference in the frequency of an allele or genotype of the polymorphism under test between the two groups indicates that the genetic marker may increase risk of the disease or likelihood of the trait, or be in linkage disequilibrium with a polymorphism which does. (wikipedia.org)
  • The model predicts that the genetic variance, and hence the heritability, in the trait is contributed by mutations at low frequency in the population, unless the mean strength of selection of mutations that affect the trait is very small or weakly selected mutations tend to contribute disproportionately to the trait compared with strongly selected mutations. (pnas.org)
  • We computed voxel-wise heritability estimates for fractional anisotropy in over 1,100 DTI scans, and used the results to threshold FA images from new studies. (springer.com)
  • Heritability of alcohol drinking is estimated to be ∼40% ( 4 ), and its genetic component gradually grows in importance as individuals age ( 3 , 5 ). (pnas.org)
  • The concentration of 25-hydroxyvitamin D has been reported to be highly heritable, with heritability estimates of 50-80% from classical twin studies 9 , 10 . (nature.com)
  • To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). (diva-portal.org)
  • Heritability of the severity of diabetic retinopathy: the FIND-Eye study. (semanticscholar.org)
  • On the basis of these theoretical calculations and their experimental validation, our results suggest that pooling-based GWA studies are a logical first step for determining whether major genetic associations exist in diseases with high heritability. (uzh.ch)
  • The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). (diva-portal.org)
  • Eight variants were chosen for meta-analysis, and significance was shown for the variants collagen, type I, α 1 ( COL1A1 ) G2046T (all genetic models), COL1A1 G-1997T (allele contrast and dominant model) and integrin β-chain β 3 ( ITGB3 ) T176C (recessive and additive models). (biomedcentral.com)
  • We observed an association with recurrence for an intergenic variant at 18q22.1 with an odds ratio of 1.7 (95% confidence interval, 1.2-2.6) per copy of the minor allele. (ovid.com)
  • The rs7903146 T at-risk allele associates with decreased BMI and earlier age at diagnosis in the type 2 diabetic subjects (P = 8.0 x 10(-3) and P = 3.8 x 10(-4), respectively), which is supported by quantitative family-based association tests. (cun.es)
  • In addition, power for detecting significance of h when the study conforms to HWE rule increases with the degree of dominance and to some extent is related to the mutant allele frequency. (biomedcentral.com)
  • One of the major challenges of the personal genomic era will be knowing exactly which (if any) of the millions of genetic variants present in your genome are likely to actually have an impact on your health. (scienceblogs.com)
  • Furthermore, identification of genetic variants that have similar effect size and direction across ethnicities, despite the interethnic differences in background risk, can narrow associated genomic regions and provide robust, reliable findings that are more likely to be proximal to the functional variant responsible. (ahajournals.org)
  • S/he will develop skills and experience in managing and analysing very large genetic, phenotypic and linked datasets, learn advanced computational and statistical skills and have the opportunity for publication in high impact journals. (findaphd.com)
  • BACKGROUND: The phenotypic heterogeneity of sickle cell disease is likely the result of multiple genetic factors and their interaction with the sickle mutation. (rti.org)
  • The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. (uzh.ch)
  • Genetic association is when one or more genotypes within a population co-occur with a phenotypic trait more often than would be expected by chance occurrence. (wikipedia.org)
  • Narrative reviews rarely state how studies were selected for inclusion, how (or whether) their quality was assessed, or how the findings from multiple studies were synthesized in order to draw conclusions. (prolekare.cz)
  • In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. (diva-portal.org)
  • The available data are not consistent with more than modest associations between these candidate cytokine variant alleles and NEC in preterm infants. (bmj.com)
  • A differential magnitude of effect in large versus small studies (that is, indication of publication bias) was detected for the variant COL1A1 G2046T. (biomedcentral.com)
  • However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity. (sigmaaldrich.com)
  • Can be expensive, especially if it is a prospective cohort study. (phgfoundation.org)
  • In the study, researchers followed 851 female Norwegian and Finnish elite athletes from team sports, recording ACL injuries acquired before inclusion in the cohort and any new complete ACL injuries through 2015. (ptproductsonline.com)
  • In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.pin the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. (nottingham.ac.uk)
  • For several decades, researchers at the National Institute on Deafness and Other Communication Disorders (NIDCD) have been leading an effort to understand the genetic underpinnings of enlarged vestibular aqueducts (EVA), a condition associated with early hearing loss in children, and in some cases, thyroid problems in the teenage years. (vestibular.org)
  • To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. (nottingham.ac.uk)
  • To examine these topics I performed a simulation study in which I simulated data set with 1,000 genotypes and 1,000 individuals. (helsinki.fi)
  • Genetic association studies today are based on the principle that genotypes can be compared "directly", i.e. with the sequences of the actual genomes or exomes via whole genome sequencing or whole exome sequencing. (wikipedia.org)
  • In genetic case-control studies, the frequency of alleles or genotypes is compared between the cases and controls. (wikipedia.org)
  • On the interpretation of genetic association studies. (harvard.edu)
  • Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. (uio.no)