Ignite Creation Date:
2024-05-05 @ 10:23 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00005269
Status:
COMPLETED
Last Update Posted:
2021-10-01
First Post:
2000-05-25
Brief Title:
Family Blood Pressure Program - GENOA
Sponsor:
The University of Texas Health Science Center Houston
Organization:
The University of Texas Health Science Center Houston
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To localize identify and evaluate common polymorphic variation in genes involved in determining interindividual differences in blood pressure BP levels and essential hypertension status in three racial groups African-Americans Mexican-Americans and Non-Hispanic Whites The study consists of a six grant network which in turn is part of an NHLBI initiative the Family Blood Pressure Program FBPP consisting of four networks
Detailed Description:
BACKGROUND
Hypertension a complex disease involving the interplay of genetic and environmental factors affects an estimated 50 million Americans and is a major predisposing factor for myocardial infarction vascular disease stroke and renal failure It has been estimated from segregation analysis and twin studies that approximately 45 percent of the interindividual differences in blood pressure are accounted for by genetic differences The identification of the genes whose variants contribute to high blood pressure will have far-reaching effects on our understanding of the pathophysiology of the circulation and may suggest new preventive measures and rational therapeutic approaches
One of the principal advantages of the genetic approach is that it identifies primary molecular defects As a result it will be possible to stratify the general hypertensive population into subgroups based on genotype and intermediate phenotype and thereby evaluate preventive strategies and therapeutic approaches in more homogeneous groups In addition the identification of hypertensive genes also provides the basis for an understanding of the interactions between genes and environmental factors It is very likely that particular environmental variables exert their effects only in the presence of certain genotypes
Until recently the techniques for dissecting the genetic determinants of high blood pressure were not available or were not developed to an extent that would make the Family Blood Pressure Program initiative feasible However several recent advances in technology and analytical methods together with the rapid construction of genetic maps have substantially improved the chances of detecting these genetic factors
The concept for the Family Blood Pressure Program was conceived in the Report of the Expert Panel on Genetic Strategies for Heart Lung and Blood Diseases The initiative was approved by the Arteriosclerosis Hypertension and Lipid Metabolism Advisory Committee AHLMAC in March 1993 The genetic-epidemiological aspects were approved by the Clinical Applications and Prevention Advisory Committee CAPAC in February 1993 The Request for Applications was released in March 1994 Awards were made in September 1995
DESIGN NARRATIVE
GENOA the Genetic Epidemiology Network of Arteriopathy consists of a network of three field centers and biochemical and genetic core labs to study the common polymorphic genetic variations to determine individual differences in blood pressure and essential hypertension in 1500 sibling pairs in three racial groups Linkage analyses are performed using an extensive array of candidate genes and anonymous markers throughout the genome
Each collaborating investigator is responsible for an essential element of the network Eric Boerwinkle for genotyping and linkage analyses Robert Ferrell for genotyping Craig Hanis for recruiting Mexican-Americans Richard Hutchinson for recruiting African-Americans Sharon Kardia for cladistic and prediction analyses and data management and Stephen Turner for recruiting Non-Hispanic whites and measuring physiologic variables Between 1995 and 2000 the network carried out five specific aims to localize and characterize the genetic determinants of high blood pressure Aim 1 used robust sibling pair linkage methods in 500 hypertensive sibling pairs in each racial group a total of 1500 sibling pairs to localize genes influencing interindividual differences in the occurrence of essential hypertension Aims 2 and 3 took advantage of previously collected blood pressure and intermediate predictor trait data from 1488 normotensive sibling pairs from the Rochester Family Heart Study to localize genes contributing to essential hypertension The linkage analyses Aims 1-3 used both an extensive array of candidate genes and a large number of anonymous markers throughout the genome Aim 4 used multiple diallelic sequence polymorphisms and cladistic analyses within a linked gene to identify haplotypes for further DNA sequencing in order to identify candidate functional DNA sequence variation contributing to interindividual differences in BP levels and essential hypertension status Aim 5 evaluated the ability of candidate functional DNA sequence variation to predict essential hypertension status in the three racial groups
The study was renewed in September 2000 to pursue two lines of investigation The first was to identify and characterize genes contributing to atherosclerotic coronary heart disease using electron beam computed tomography EBCT to quantify coronary artery calcification as a measure of preclinical disease Robust sibling-pair linkage methods were used to determine whether any of the more than 375 highly polymorphic tandem repeat marker loci spanning the genome were linked to genes influencing EBCT measures of coronary artery calcification in at least 500 GENOA sibships from Rochester Minnesota Association analysis was used to determine whether biallelic markers of DNA sequence variation in candidate genes identified by GENOA or others to influence blood pressure level or diagnostic category also influence EBCT measures of coronary artery calcification in at least 500 GENOA participants from Rochester Minnesota The second line of investigation extended analytical methods linkage disequilibrium regression and combinatorial partitioning to more finely localize positional candidate genes and loci and to identifying gene-gene and gene-environment interaction effects influencing the measured Family Blood Pressure Program and GENOA phenotypes
In the next phase of the FBPP extending the study through FY 2008 a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world In Aim 1 the intestigators will build maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension its risk factors and its complications In Aim 2 they will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes In Aim 3 they will use a combination of bioinformatics a dense array of SNPs and state-of-the-art data analysis to follow-up regions of interest and identify the underlying hypertension genes The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase In Aim 4 they will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension including left ventricular mass and microalbuminuria It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension including its risk factors complications and response to treatment
Hypertension a complex disease involving the interplay of genetic and environmental factors affects an estimated 50 million Americans and is a major predisposing factor for myocardial infarction vascular disease stroke and renal failure It has been estimated from segregation analysis and twin studies that approximately 45 percent of the interindividual differences in blood pressure are accounted for by genetic differences The identification of the genes whose variants contribute to high blood pressure will have far-reaching effects on our understanding of the pathophysiology of the circulation and may suggest new preventive measures and rational therapeutic approaches
One of the principal advantages of the genetic approach is that it identifies primary molecular defects As a result it will be possible to stratify the general hypertensive population into subgroups based on genotype and intermediate phenotype and thereby evaluate preventive strategies and therapeutic approaches in more homogeneous groups In addition the identification of hypertensive genes also provides the basis for an understanding of the interactions between genes and environmental factors It is very likely that particular environmental variables exert their effects only in the presence of certain genotypes
Until recently the techniques for dissecting the genetic determinants of high blood pressure were not available or were not developed to an extent that would make the Family Blood Pressure Program initiative feasible However several recent advances in technology and analytical methods together with the rapid construction of genetic maps have substantially improved the chances of detecting these genetic factors
The concept for the Family Blood Pressure Program was conceived in the Report of the Expert Panel on Genetic Strategies for Heart Lung and Blood Diseases The initiative was approved by the Arteriosclerosis Hypertension and Lipid Metabolism Advisory Committee AHLMAC in March 1993 The genetic-epidemiological aspects were approved by the Clinical Applications and Prevention Advisory Committee CAPAC in February 1993 The Request for Applications was released in March 1994 Awards were made in September 1995
DESIGN NARRATIVE
GENOA the Genetic Epidemiology Network of Arteriopathy consists of a network of three field centers and biochemical and genetic core labs to study the common polymorphic genetic variations to determine individual differences in blood pressure and essential hypertension in 1500 sibling pairs in three racial groups Linkage analyses are performed using an extensive array of candidate genes and anonymous markers throughout the genome
Each collaborating investigator is responsible for an essential element of the network Eric Boerwinkle for genotyping and linkage analyses Robert Ferrell for genotyping Craig Hanis for recruiting Mexican-Americans Richard Hutchinson for recruiting African-Americans Sharon Kardia for cladistic and prediction analyses and data management and Stephen Turner for recruiting Non-Hispanic whites and measuring physiologic variables Between 1995 and 2000 the network carried out five specific aims to localize and characterize the genetic determinants of high blood pressure Aim 1 used robust sibling pair linkage methods in 500 hypertensive sibling pairs in each racial group a total of 1500 sibling pairs to localize genes influencing interindividual differences in the occurrence of essential hypertension Aims 2 and 3 took advantage of previously collected blood pressure and intermediate predictor trait data from 1488 normotensive sibling pairs from the Rochester Family Heart Study to localize genes contributing to essential hypertension The linkage analyses Aims 1-3 used both an extensive array of candidate genes and a large number of anonymous markers throughout the genome Aim 4 used multiple diallelic sequence polymorphisms and cladistic analyses within a linked gene to identify haplotypes for further DNA sequencing in order to identify candidate functional DNA sequence variation contributing to interindividual differences in BP levels and essential hypertension status Aim 5 evaluated the ability of candidate functional DNA sequence variation to predict essential hypertension status in the three racial groups
The study was renewed in September 2000 to pursue two lines of investigation The first was to identify and characterize genes contributing to atherosclerotic coronary heart disease using electron beam computed tomography EBCT to quantify coronary artery calcification as a measure of preclinical disease Robust sibling-pair linkage methods were used to determine whether any of the more than 375 highly polymorphic tandem repeat marker loci spanning the genome were linked to genes influencing EBCT measures of coronary artery calcification in at least 500 GENOA sibships from Rochester Minnesota Association analysis was used to determine whether biallelic markers of DNA sequence variation in candidate genes identified by GENOA or others to influence blood pressure level or diagnostic category also influence EBCT measures of coronary artery calcification in at least 500 GENOA participants from Rochester Minnesota The second line of investigation extended analytical methods linkage disequilibrium regression and combinatorial partitioning to more finely localize positional candidate genes and loci and to identifying gene-gene and gene-environment interaction effects influencing the measured Family Blood Pressure Program and GENOA phenotypes
In the next phase of the FBPP extending the study through FY 2008 a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world In Aim 1 the intestigators will build maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension its risk factors and its complications In Aim 2 they will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes In Aim 3 they will use a combination of bioinformatics a dense array of SNPs and state-of-the-art data analysis to follow-up regions of interest and identify the underlying hypertension genes The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase In Aim 4 they will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension including left ventricular mass and microalbuminuria It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension including its risk factors complications and response to treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 5U01HL054481-13 | NIH | None | httpsreporternihgovquickSearch5U01HL054481-13 |