Segregation/Linkage Analysis for Hypertension

2014-08-27 03:58:00 | BioPortfolio


To determine the genetic components of hypertension using a series of simulation experiments designed to determine the power and validity of the then recently developed methods of segregation and linkage analysis.



There are two general hypotheses about the nature of the genetic component of hypertension. A single gene hypothesis visualizes hypertension as a specific disease entity determined by an autosomal dominant or incompletely dominant allele with little environmental effect. A polygenic hypothesis views hypertension as determined by a large number of genetic and environmental factors operating independently with roughly equal contributions. The evidence supporting the single gene hypothesis is based primarily on bimodal and trimodal distributions of blood pressure in the population. It has been suggested that the bimodal or trimodal distributions are the result of ascertainment bias. The evidence supporting the polygenic model is based on several studies where the distribution of blood pressure is unimodal and often skewed toward higher values in both the population and in first degree relatives of hypertensive individuals. These skewed distributions can be approximately normalized using log transformations.

In this study, a particular effort was made to detect major genes. A major gene is said to exist in a particular sample if an appreciable amount of the variability of a trait in that sample is due to segregation of alleles at a single locus. The presence of a major gene does not preclude the existence of other genetic or environmental effects. In the last decade three general models have been proposed to detect the presence of a major gene. The transmission probability model is a general model for the genetic analysis of pedigree data which tests for Mendelian segregation ratios and is a generalization of the traditional methods of segregation analysis. This model has little power to differentiate between single gene and polygenic inheritance although it may be able to detect some kinds of non-single gene transmission. This method has been extended to allow analysis of multivariate traits, testing of a wide variety of hypotheses concerning modes of transmission and various ascertainment corrections. Major genes identified with this model include hypercholesterolemia, dopamine-beta-hydroxylase, and catechol-o-methytransferase.

The mixed model includes both a single locus and a multi-locus component and is designed to distinguish between the two. The model assumes that all transmission from one generation to the next that cannot be accounted for by classical polygenic inheritance is due to segregation of alleles at a single locus. It is ideal for detecting a major gene in the presence of polygenic inheritance provided that no other type of transmission is occurring. This model has been extended to include an environmental correlation among sibs. Major loci identified with this model include PTC, IgE and congenital glaucoma. The unified model is a mixed model with the single locus component parameterized in terms of transmission probabilities, and is a combination of the two previous models. Several research groups have developed methodologies to overcome the computational difficulties presented by this combined model.


The study was divided into two parts, the analysis of the methodologies and the application of the methodologies in the genetic analysis of hypertension. In the first part of the study, the power, robustness, and validity of three genetic models of segregation and linkage analysis were considered: the transmission probability model; the mixed model; and the unified model which was also a mixed model with the single locus component parameterized in terms of transmission probabilities. The methods of segregation and linkage analysis found to be most satisfactory were then applied to the analysis of data on five large pedigrees in collaboration with Wright State University and to the analysis of ten large pedigrees ascertained as part of the Bogalusa Heart Study. A determination was made of the effects of partitioning large families into nuclear families and performing segregation and linkage on these nuclear families.

Study Design

Observational Model: Natural History


Cardiovascular Diseases




National Heart, Lung, and Blood Institute (NHLBI)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:58:00-0400

Clinical Trials [1162 Associated Clinical Trials listed on BioPortfolio]

Cardiovascular Diseases in HIV-infected Subjects (HIV-HEART Study)

Human immunodeficiency virus (HIV) infection has been associated with a variety of cardiovascular diseases. Even most industrialised countries exhibit a growing and aging population of HIV...

The Effects of Aerobic Exercise in Microvascular Endothelium Function in Patients With Cardiovascular Diseases

This study evaluates the effects of different volumes of aerobic exercise training in cardiovascular parameters of patients with cardiovascular diseases enrolled in a cardiac rehabilitatio...

Development, Testing, and Validation of A Protocol To Assess Cardiovascular Reactivity in Human Populations

To develop a comprehensive protocol for assessing cardiovascular reactivity to stressors, for use in epidemiological and clinical investigations of cardiovascular diseases in healthy popul...

Cardiovascular Diseases in the Silesian Region in Poland.

The Silesian Cardiovascular Database is an observational study of all patients hospitalized due to cardiovascular diseases. The date include information on the clinical characteristics, tr...

Early Detection of Atherosclerosis: a Randomized Trial in the Primary Prevention of Cardiovascular Diseases.

The incidence of cardiovascular diseases is still high and further efforts should be done in primary prevention. The main objective is to quantify the burden of subclinical atherosclerosis...

PubMed Articles [11831 Associated PubMed Articles listed on BioPortfolio]

Risk factors of cardiovascular disease and its recommendations in Pakistani context.

Cardiovascular diseases possess a major cause for fatality and disability the world over. Since last several decades, the rates of cardiovascular diseases-related deaths have decreased in a number of ...

Association between alexithymia and risk of incident cardiovascular diseases in the SUpplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) Cohort.

Although alexithymia has been suggested to be associated with cardiovascular diseases, studies are scarce and a causal relationship is questionable. This study explored the prospective association bet...

Lipidomic insight into cardiovascular diseases.

Cardiovascular disease is a primary cause of mortality worldwide. Therefore, it is of major interest to identify sensitive molecular markers that predict cardiovascular events and point to therapeutic...

Efficacy of primary prevention for atherosclerosis-induced diseases in patients with high cardiovascular risk in Russia and other European countries (Part 1).

Evaluation of the effectiveness of risk management in persons with high cardiovascular risk is an important element in reducing the death rate of the population from cardiovascular diseases (CVD).

MicroRNAs as Biomarkers of Cardiovascular Diseases.

The fact that microRNAs play an important role in the development and pathogenesis of cardiovascular disease is beyond doubt. This article provides a brief overview of recent data that relate to micro...

Medical and Biotech [MESH] Definitions

Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.

Methods and procedures for the diagnosis of diseases or dysfunction of the cardiovascular system or its organs or demonstration of their physiological processes.

Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)

Dental care for patients with chronic diseases. These diseases include chronic cardiovascular, endocrinologic, hematologic, immunologic, neoplastic, and renal diseases. The concept does not include dental care for the mentally or physically disabled which is DENTAL CARE FOR DISABLED.

Blood pressure levels that are between normotension and hypertension. Individuals with prehypertension are at a higher risk for developing cardiovascular diseases. Generally, prehypertension is defined as SYSTOLIC PRESSURE of 131-139 mm Hg and/or DIASTOLIC PRESSURE of 81-89 when the optimal is 120/80 mm Hg. For diabetics and other metabolism diseases the prehypertension is around 110-129/70-79 mm Hg.

More From BioPortfolio on "Segregation/Linkage Analysis for Hypertension"

Quick Search


Relevant Topics

Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Adempas (riociguat)
The United States Food and Drug Administration (FDA) has approved on October 8th 2013 Adempas® (riociguat) tablets for: (i) the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO* Group 4) after ...

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Searches Linking to this Trial