Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005490
Status:
COMPLETED
Last Update Posted:
2016-11-06
First Post:
2000-05-25
Brief Title:
Modeling DNA Diversity in Cardiovascular HealthDisease
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2005-02
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 identify and measure DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease that is genes involved in lipid metabolism carbohydrate metabolism and blood pressure regulation
Detailed Description:
BACKGROUND
One of the most complex and challenging problems in human biology and medicine is defining the relationship between DNA sequence variation and interindividual variation in quantitative risk factors for complex diseases having a multifactorial etiology As the knowledge about the basic human DNA sequence increases so will the need to define the range of natural variation in human populations and to explore the relationship between nucleotide diversity and phenotype variation in measures of human health
DESIGN NARRATIVE
The study was a collaborative one involving Dr Deborah Nickerson at the University of Washington Dr Kenneth Weiss at Pennsylvania State University and Dr Charles Sing of the University of Michigan Dr Nickerson identified and measured DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease She applied state-of-the-art automated fluorescence-based sequencing and high-throughput DNA genotyping methods to uncover and assess DNA sequence variation in three human populations non-Hispanic Whites from Rochester MN lowCVD risk African-Americans from Jackson MS intermediate CVD risk and non-Hispanic Whites from North KareliaFinland high CVD risk
Dr Weiss used the theoretical and statistical approaches of molecular population genetics to characterize the cumulative effects of population history on the amount distribution and structure of extant variation in 13 candidate CVD susceptibility genes in three populations His tests of linkage equilibrium and of homogeneity of the variation across several levels of stratification among individuals demographic variables parts of genes populations and among genes further sharpened the understanding of the nature of human genetic variation particularly with respect to candidate CVD susceptibility genes He made inferences about functional constraints from gene trees and from patterns of divergence among human populations and between humans and the chimpanzee Dr Weisss project provided the inferential engine that drove the sampling design and sample selection in Dr Nickersons project and provided the demographichistorical background necessary for genotype-phenotype inferences of Dr Sings project
Dr Sing developed models for the relationships between the DNA sequence variation in the 13 candidate CVD susceptibility genes identified measured and characterized in Dr Nickersons and Dr Weisss projects and variation in established quantitative risk factors for CVD including total plasma cholesterol HDL cholesterol and triglycerides and systolic and diastolic blood pressure collected from the 1500 individuals His project established which subset of DNA sequence variations in which candidate genes were associated with variation in CVD risk factors in which subset of individuals and in which of three populations His elucidation of the relationships between DNA sequence variations and variations in intermediate biological risk factor traits revealed opportunities for intervention to alter the risk of CVD and establish whether such efforts should be directed across populations within a population or at an individual
The study completion date listed in this record was obtained from the End Date entered in the old format Protocol Registration and Results System PRS
One of the most complex and challenging problems in human biology and medicine is defining the relationship between DNA sequence variation and interindividual variation in quantitative risk factors for complex diseases having a multifactorial etiology As the knowledge about the basic human DNA sequence increases so will the need to define the range of natural variation in human populations and to explore the relationship between nucleotide diversity and phenotype variation in measures of human health
DESIGN NARRATIVE
The study was a collaborative one involving Dr Deborah Nickerson at the University of Washington Dr Kenneth Weiss at Pennsylvania State University and Dr Charles Sing of the University of Michigan Dr Nickerson identified and measured DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease She applied state-of-the-art automated fluorescence-based sequencing and high-throughput DNA genotyping methods to uncover and assess DNA sequence variation in three human populations non-Hispanic Whites from Rochester MN lowCVD risk African-Americans from Jackson MS intermediate CVD risk and non-Hispanic Whites from North KareliaFinland high CVD risk
Dr Weiss used the theoretical and statistical approaches of molecular population genetics to characterize the cumulative effects of population history on the amount distribution and structure of extant variation in 13 candidate CVD susceptibility genes in three populations His tests of linkage equilibrium and of homogeneity of the variation across several levels of stratification among individuals demographic variables parts of genes populations and among genes further sharpened the understanding of the nature of human genetic variation particularly with respect to candidate CVD susceptibility genes He made inferences about functional constraints from gene trees and from patterns of divergence among human populations and between humans and the chimpanzee Dr Weisss project provided the inferential engine that drove the sampling design and sample selection in Dr Nickersons project and provided the demographichistorical background necessary for genotype-phenotype inferences of Dr Sings project
Dr Sing developed models for the relationships between the DNA sequence variation in the 13 candidate CVD susceptibility genes identified measured and characterized in Dr Nickersons and Dr Weisss projects and variation in established quantitative risk factors for CVD including total plasma cholesterol HDL cholesterol and triglycerides and systolic and diastolic blood pressure collected from the 1500 individuals His project established which subset of DNA sequence variations in which candidate genes were associated with variation in CVD risk factors in which subset of individuals and in which of three populations His elucidation of the relationships between DNA sequence variations and variations in intermediate biological risk factor traits revealed opportunities for intervention to alter the risk of CVD and establish whether such efforts should be directed across populations within a population or at an individual
The study completion date listed in this record was obtained from the End Date entered in the old format Protocol Registration and Results System PRS
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL058240 | NIH | None | httpsreporternihgovquickSearchR01HL058240 |
| R01HL058238 | NIH | None | None |
| R01HL058239 | NIH | None | None |