Cardiovascular DiseasesNCT00005158
Segregation/Linkage Analysis for Hypertension
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 100 years, men only
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Hypertension
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Jul 1982to Jun 1991
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
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.
Read the detailed description
BACKGROUND:
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.
DESIGN NARRATIVE:
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.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
- Conditions
- Cardiovascular Diseases, Heart Diseases, Hypertension
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Hypertension
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2000 (estimated)
- Study startJul 1982
- Study completionJun 1991
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005158
- Sponsor's protocol ID
- 1030
- Other IDs
- R01HL028522
- Status last verified
- Jun 2000
- First submitted
- 25 May 2000
- Last updated
- 18 Feb 2016
- Results posted
- No
Publications
Siervogel RM, Weinshilboum R, Wilson AF, Elston RC. Major gene model for the inheritance of catechol-O-methyltransferase activity in five large families. Am J Med Genet. 1984 Oct;19(2):315-23. doi: 10.1002/ajmg.1320190214.
PubMed 6594929Wilson AF, Elston RC, Siervogel RM, Weinshilboum R, Ward LJ. Linkage relationships between a major gene for catechol-o-methyltransferase activity and 25 polymorphic marker systems. Am J Med Genet. 1984 Nov;19(3):525-32. doi: 10.1002/ajmg.1320190314.
PubMed 6507499Townley RG, Bewtra A, Wilson AF, Hopp RJ, Elston RC, Nair N, Watt GD. Segregation analysis of bronchial response to methacholine inhalation challenge in families with and without asthma. J Allergy Clin Immunol. 1986 Jan;77(1 Pt 1):101-7. doi: 10.1016/0091-6749(86)90330-1.
PubMed 3944368Amos CI, Wilson AF, Rosenbaum PA, Srinivasan SR, Webber LS, Elston RC, Berenson GS. An approach to the multivariate analysis of high-density-lipoprotein cholesterol in a large kindred: the Bogalusa Heart Study. Genet Epidemiol. 1986;3(4):255-67. doi: 10.1002/gepi.1370030406.
PubMed 3744022Asamoah A, Wilson AF, Elston RC, Dalferes E Jr, Berenson GS. Segregation and linkage analyses of dopamine-beta-hydroxylase activity in a six-generation pedigree. Am J Med Genet. 1987 Jul;27(3):613-21. doi: 10.1002/ajmg.1320270314.
PubMed 3631133Amos CI, Elston RC, Srinivasan SR, Wilson AF, Cresanta JL, Ward LJ, Berenson GS. Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study. Genet Epidemiol. 1987;4(2):115-28. doi: 10.1002/gepi.1370040206.
PubMed 3108069Wilson AF, Bailey-Wilson JE, Cleton FJ, Elston RC, King MC. Linkage analysis of Dutch families at high risk for breast cancer. Genet Epidemiol Suppl. 1986;1:87-92. doi: 10.1002/gepi.1370030714. No abstract available.
PubMed 3471674Crowe RR, Noyes R Jr, Wilson AF, Elston RC, Ward LJ. A linkage study of panic disorder. Arch Gen Psychiatry. 1987 Nov;44(11):933-7. doi: 10.1001/archpsyc.1987.01800230013003.
PubMed 3675131Asamoah A, Wyatt RJ, Julian BA, Quiggins PA, Wilson AF, Elston RC. A major gene model for the familial aggregation of plasma IgA concentration. Am J Med Genet. 1987 Aug;27(4):857-66. doi: 10.1002/ajmg.1320270413.
PubMed 3480689Wilson AF, Elston RC, Siervogel RM, Tran LD. Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus. Am J Hum Genet. 1988 Jan;42(1):160-6.
PubMed 3422127Hill EM, Wilson AF, Elston RC, Winokur G. Evidence for possible linkage between genetic markers and affective disorders. Biol Psychiatry. 1988 Dec;24(8):903-17. doi: 10.1016/0006-3223(88)90225-9.
PubMed 3233232Tanna VL, Wilson AF, Winokur G, Elston RC. Possible linkage between alcoholism and esterase-D. J Stud Alcohol. 1988 Sep;49(5):472-6. doi: 10.15288/jsa.1988.49.472.
PubMed 3216652Wilson AF, Cohen JC. Hypotheses for testing deviations from random integration: evidence for nonrandom retroviral integration. Genomics. 1988 Aug;3(2):137-42. doi: 10.1016/0888-7543(88)90144-9.
PubMed 3224979Wilson AF, Tanna VL, Winokur G, Elston RC, Hill EM. Linkage analysis of depression spectrum disease. Biol Psychiatry. 1989 Jun;26(2):163-75. doi: 10.1016/0006-3223(89)90020-6.
PubMed 2736265Amos CI, Elston RC, Wilson AF, Bailey-Wilson JE. A more powerful robust sib-pair test of linkage for quantitative traits. Genet Epidemiol. 1989;6(3):435-49. doi: 10.1002/gepi.1370060306.
PubMed 2753353
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Segregation/Linkage Analysis for Hypertension
- ClinicalTrials.gov ID
- NCT00005158
- Acronym / sponsor ID
- 1030
- Conditions
- Cardiovascular Diseases, Heart Diseases, Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Jul 1982
- Study completion
- Jun 1991 (actual)
- First posted
- 26 May 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BACKGROUND:
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.
DESIGN NARRATIVE:
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.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Study design
Who may qualify
- Ages
- Up to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2016.
- Background: PubMed 6594929Siervogel RM, Weinshilboum R, Wilson AF, Elston RC. Major gene model for the inheritance of catechol-O-methyltransferase activity in five large families. Am J Med Genet. 1984 Oct;19(2):315-23. doi: 10.1002/ajmg.1320190214.
- Background: PubMed 6507499Wilson AF, Elston RC, Siervogel RM, Weinshilboum R, Ward LJ. Linkage relationships between a major gene for catechol-o-methyltransferase activity and 25 polymorphic marker systems. Am J Med Genet. 1984 Nov;19(3):525-32. doi: 10.1002/ajmg.1320190314.
- Background: PubMed 3944368Townley RG, Bewtra A, Wilson AF, Hopp RJ, Elston RC, Nair N, Watt GD. Segregation analysis of bronchial response to methacholine inhalation challenge in families with and without asthma. J Allergy Clin Immunol. 1986 Jan;77(1 Pt 1):101-7. doi: 10.1016/0091-6749(86)90330-1.
- Background: PubMed 3744022Amos CI, Wilson AF, Rosenbaum PA, Srinivasan SR, Webber LS, Elston RC, Berenson GS. An approach to the multivariate analysis of high-density-lipoprotein cholesterol in a large kindred: the Bogalusa Heart Study. Genet Epidemiol. 1986;3(4):255-67. doi: 10.1002/gepi.1370030406.
- Background: PubMed 3631133Asamoah A, Wilson AF, Elston RC, Dalferes E Jr, Berenson GS. Segregation and linkage analyses of dopamine-beta-hydroxylase activity in a six-generation pedigree. Am J Med Genet. 1987 Jul;27(3):613-21. doi: 10.1002/ajmg.1320270314.
- Background: PubMed 3108069Amos CI, Elston RC, Srinivasan SR, Wilson AF, Cresanta JL, Ward LJ, Berenson GS. Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study. Genet Epidemiol. 1987;4(2):115-28. doi: 10.1002/gepi.1370040206.
- Background: PubMed 3471674Wilson AF, Bailey-Wilson JE, Cleton FJ, Elston RC, King MC. Linkage analysis of Dutch families at high risk for breast cancer. Genet Epidemiol Suppl. 1986;1:87-92. doi: 10.1002/gepi.1370030714. No abstract available.
- Background: PubMed 3675131Crowe RR, Noyes R Jr, Wilson AF, Elston RC, Ward LJ. A linkage study of panic disorder. Arch Gen Psychiatry. 1987 Nov;44(11):933-7. doi: 10.1001/archpsyc.1987.01800230013003.
- Background: PubMed 3480689Asamoah A, Wyatt RJ, Julian BA, Quiggins PA, Wilson AF, Elston RC. A major gene model for the familial aggregation of plasma IgA concentration. Am J Med Genet. 1987 Aug;27(4):857-66. doi: 10.1002/ajmg.1320270413.
- Background: PubMed 3422127Wilson AF, Elston RC, Siervogel RM, Tran LD. Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus. Am J Hum Genet. 1988 Jan;42(1):160-6.
- Background: PubMed 3233232Hill EM, Wilson AF, Elston RC, Winokur G. Evidence for possible linkage between genetic markers and affective disorders. Biol Psychiatry. 1988 Dec;24(8):903-17. doi: 10.1016/0006-3223(88)90225-9.
- Background: PubMed 3216652Tanna VL, Wilson AF, Winokur G, Elston RC. Possible linkage between alcoholism and esterase-D. J Stud Alcohol. 1988 Sep;49(5):472-6. doi: 10.15288/jsa.1988.49.472.
Related trials for Cardiovascular Diseases
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure
Recruiting
Delay AvoIding Primary Evaluation for ThRombectomy of Acute StrokE Patients With Large Vessel OCclusion in the Angiography SuiTe
Stroke, Acute
Active, not recruitingObservational study
REdo Transcatheter Aortic VALVE Implantation for the Management of Transcatheter Aortic Valve Failure
Aortic Valve Stenosis
RecruitingPhase 1/2
A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma
Relapsed/Refractory Multiple Myeloma
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005158, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2016.