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Richard S Cooper

Publications and source records attributed to Richard S Cooper.

At least 55 records · Page 3Linked to original sources
PubMed2003

Genomics and medicine: distraction, incremental progress, or the dawn of a new age?

The technology of molecular genetics has profoundly altered the conduct of biomedical research. An entire universe of problems that in the past had been addressed only through conjecture, including whole genome analysis, can now be studied directly. The rapidity and scope of these changes in research capacity have in turn led to speculation that medicine will be radically altered by the application of genomics to everyday practice. To date, gene therapy and several new tests for genetic susceptibility have been successfully implemented, although their impact on medicine as a whole remains very limited and their future contribution is hotly contested. The potential of molecular genetics, like all technology, must be evaluated on the basis of established principles of clinical and epidemiologic research. The rhetoric of some enthusiasts focuses instead on an optimistic best-case scenario of the future of DNA science, and many of their most far-reaching claims cannot be substantiated on the basis of what is currently known. The tension between the long-term goal of public health and medicine to identify and remove the causes of ill health, in contrast to the development of technological innovations that can cure disease or identify individual susceptibility, emerges as a major theme in this debate.

Culture↗
PubMed2003

Linkage disequilibrium analysis of the renin-angiotensin system genes.

The genes of the renin-angiotensin system (RAS) are important candidates to confer susceptibility to cardiovascular diseases. A large number of association studies between cardiovascular traits and the polymorphisms in RAS have been conducted, although inconsistent results are often reported. The patterns of linkage disequilibrium in RAS genes have also been reported in different populations. However, our understanding of the genetic architecture underlying the RAS is still limited despite rapid progress in empiric studies regarding the patterns of the human genome as a whole. In this review, the linkage disequilibrium among the polymorphisms within the four RAS genes and current association analyses involving the RAS are discussed, as well as some of the gaps of knowledge and possible solutions.

Cardiovascular Diseases↗
PubMed2003

A genome-wide linkage analysis investigating the determinants of blood pressure in whites and African Americans.

Evidence for genomic regions influencing systolic and diastolic blood pressure (BP) were assessed in a whole genome linkage analysis in 211 African American and 160 white families as part of the GenNet network of the National Heart, Lung and Blood Institute-sponsored Family Blood Pressure Program. Multipoint regression and variance components linkage methods were used to analyze 372 polymorphic markers. Statistically compelling evidence for linkage (P values .0057 and .00023, respectively) was found on chromosome 1. Our results support the idea that BP regulation is most likely governed by multiple genetic loci, each with a relatively weak effect on BP in the population at large.

Adult↗
PubMed2003

A meta-analysis of genome-wide linkage scans for hypertension: the National Heart, Lung and Blood Institute Family Blood Pressure Program.

BACKGROUND: Four multicenter Networks (GenNet, GENOA, HyperGEN, SAPPHIRe) form the National Heart, Lung and Blood Institute Family Blood Pressure Program (FBPP), to search for hypertension/blood pressure (BP) genes. The networks used different family designs and targeted multiple ethnic groups, using standardized protocols and definitions. Linkage genome scans were done on samples within each network (N = 6245 relatives). METHODS: The evidence was synthesized using meta-analysis. RESULTS: Combining ethnic groups, no region reached LOD >2, but several small peaks were identified, including chromosome 2p where two other recent reports find hypertension linkage. CONCLUSIONS: No regions show uniformly large effects on BP/hypertension in all populations.

Chromosome Mapping↗
PubMed2003

Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program.

A combined analysis of genome scans was performed for adult height in the NHLBI Family Blood Pressure Program. Height data were available on 6752 individuals. Linkage analysis was performed first separately for each of the eight ethnic groups in the four networks using the variance component method. To increase the power to detect the common genetic components affecting height for all the individuals, a linkage analysis was performed subsequently for the combined data set by pooling the average allele-sharing IBD () for all groups. By combining the data, we replicated evidence for a QTL influencing adult height on chromosome 7 (7q31) (LOD=2.46), which has been reported in two previous studies. Suggestive linkage (LOD>1) was found in another six regions in our combined analysis. Evidence for linkage for two of these regions (2p12, 20p11) has also been reported previously.

Adult↗
PubMed2003

An association study of angiotensinogen polymorphisms with serum level and hypertension in an African-American population.

OBJECTIVE: To evaluate the association of angiotensinogen (AGT) gene with AGT level and hypertension based on the overall genetic variation of the AGT gene in among African-Americans. METHODS: All non-rare single nucleotide polymorphisms (SNPs) in AGT were identified by resequencing 24 individuals. Five tagging SNPs were selected based on the pairwised linkage disequilibrium (LD) pattern and were genotyped in 284 individuals. Association studies of AGT level and hypertension were performed using these five tagging SNPs. RESULTS: No significant association with AGT level or hypertension was found in analyses of each of the five single SNPs. However, one of the haplotypes defined by these five SNPs was significantly associated with AGT level (P = 0.046), although this haplotype was not associated with hypertension. CONCLUSIONS: Identification of genetic polymorphisms associated with risk of hypertension has been frustratingly difficult. Two strategies adopted to improve precision are the use of intermediate phenotypes and summarization of genetic information using haplotypes. These strategies appeared to yield a modest increase in precision at the AGT locus with respect to the physiological intermediate, but did not lead to significant association of the molecular markers with hypertension. Additional research is required to increase confidence in haplotype mapping as an epidemiological analysis tool.

Adult↗
PubMed2003

Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system: findings from the family blood pressure program.

Association studies of candidate genes with complex traits have generally used one or a few single nucleotide polymorphisms (SNPs), although variation in the extent of linkage disequilibrium (LD) within genes markedly influences the sensitivity and precision of association studies. The extent of LD and the underlying haplotype structure for most candidate genes are still unavailable. We sampled 193 blacks (African-Americans) and 160 whites (European-Americans) and estimated the intragenic LD and the haplotype structure in four genes of the renin-angiotensin system. We genotyped 25 SNPs, with all but one of the pairs spaced between 1 and 20 kb, thus providing resolution at small scale. The pattern of LD within a gene was very heterogeneous. Using a robust method to define haplotype blocks, blocks of limited haplotype diversity were identified at each locus; between these blocks, LD was lost owing to the history of recombination events. As anticipated, there was less LD among blacks, the number of haplotypes was substantially larger, and shorter haplotype segments were found, compared with whites. These findings have implications for candidate-gene association studies and indicate that variation between populations of European and African origin in haplotype diversity is characteristic of most genes.

Adult↗
PubMed2003

Body composition of children in south-western Nigeria: validation of bio-electrical impedance analysis.

Bio-electrical impedance analysis (BIA) is a non-invasive method of estimating body composition and has the potential to be useful in clinics and for nutrition and health-related research in Africa. We sought to validate BIA for use among a Yoruba population in south-western Nigeria and to use BIA to assess the body composition of a healthy cohort of children. Total body water (TBW) was measured in 92 individuals (53 adults and 39 children) using deuterium dilution; height, weight and resistance were measured by BIA. Multiple regression analysis was used to develop prediction equations for TBW among children only or among all participants. Independent covariates tested in the regression models included the impedance index (height(2)/resistance), weight, age and gender with TBW as the dependent variable. Depending on the model used, between 97% (root MSE=0.7 kg ) and 99% (root MSE=0.7 kg) of the variance observed in TBW could be explained by the impedance index, weight and/or gender; age, however, was not significant in any model. In a separate cohort of 69 children, 5-8 years old, anthropometrics were measured and TBW was estimated using the developed equations. Body composition data are presented by gender and age group. BIA was validated for use among Nigerian children and adults and provides a potentially important tool for research.

Adolescent↗
PubMed2003

High blood pressure: the foundation for epidemic cardiovascular disease in African populations.

High-blood pressure is a powerful independent risk factor for death from heart disease and stroke. It is also a common clinical condition affecting more than 600 million persons worldwide and seen in nearly all populations. Although reliable, large-scale, population-based data on high blood pressure in sub-Saharan Africa (SSA) are limited, recent studies provide important and worrisome findings in both epidemiology and clinical outcomes. Although overall hypertension prevalence is between 10%-15%, prevalence rates as high as 30%-32% have been reported in middle-income urban and some rural areas. Importantly, hypertension awareness, treatment, and control rates as low as 20%, 10%, and 1%, respectively have also been found. Stroke has been by far the most common clinical sequela. In most SSA settings, hypertension control assumes a relatively low priority and little experience exists in implementing sustainable and successful programs for drug treatment. Rapid urbanization and transition from agrarian life to the wage-earning economy of city life continue to fuel increases in average blood pressure levels and prevalence of hypertension. Although the true burden of high blood pressure in sub-Saharan Africa remains largely unmeasured, compelling preliminary evidence suggests that it is the foundation for epidemic cardiovascular disease in Africa and already contributes substantively to death and disability from stroke, heart failure, and kidney failure in this region. Success in limiting this epidemic in SSA will depend heavily on the implementation of sustainable and aggressive population-based programs for high blood pressure awareness, prevention, treatment, and control. It will be critical to obtain investments in improved surveillance and program-relevant research to provide the evidence base for policy development and effective hypertension prevention and control.

Africa South of the Sahara↗
PubMed2002

Markers that discriminate between European and African ancestry show limited variation within Africa.

Markers informative for ancestry are necessary for admixture mapping and improving case-control association analyses. In particular, African Americans are an admixed population for which genetic studies require accurately evaluating admixture. This will require markers that can be used in African Americans to determine if a given genomic region is of European or African ancestry. This report shows that, despite studies indicating high intra-African sequence variation, markers with large inter-ethnic differences have only small variations in allele distribution among divergent African populations and should be valuable for evaluating admixture in complex disease genetic studies.

Africa↗
PubMed2002

Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients.

OBJECTIVES: This study was undertaken to determine whether enalapril had comparable efficacy in black and white patients with asymptomatic left ventricular dysfunction (ALVD) in preventing the development of symptomatic heart failure (HF). BACKGROUND: Recent studies have suggested that black patients with HF due to systolic dysfunction may derive less benefit than white patients with HF when treated with the same medication. METHODS: This is a post hoc analysis of the 4,054 black and white participants of the Studies of Left Ventricular Dysfunction Prevention Trial. RESULTS: Randomization to enalapril was associated with a comparable reduction in the relative risk of the development of symptomatic HF in black (relative risk [RR] 0.67, 95% confidence interval [CI] 0.49, 0.92, p = 0.01) and white patients (RR 0.61, 95% CI 0.53, 0.70, p < 0.001). Treatment with enalapril was also associated with a comparable reduction in the risk of the development of HF requiring medical therapy and the composite end point of death or development of HF in black and white patients. Black as compared with white patients with ALVD were at increased risk of the development of symptomatic HF (RR 1.81, 95% CI 1.51, 2.17, p < 0.001) despite adjustment for available measures of disease severity. CONCLUSIONS: Despite the increased absolute risk in black patients compared with white patients for the progression of ALVD, enalapril was equally efficacious in reducing the risk of progression of ALVD in these two ethnic groups.

Black or African American↗
PubMed2002

A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program.

A combined analysis of genome scans for obesity was undertaken using the interim results from the National Heart, Lung, and Blood Institute Family Blood Pressure Program. In this research project, four multicenter networks of investigators conducted eight individual studies. Data were available on 6,849 individuals from four ethnic groups (white, black, Mexican American, and Asian). The sample represents the largest single collection of genomewide scan data that has been analyzed for obesity and provides a test of the reproducibility of linkage analysis for a complex phenotype. Body mass index (BMI) was used as the measure of adiposity. Genomewide linkage analyses were first performed separately in each of the eight ethnic groups in the four networks, through use of the variance-component method. Only one region in the analyses of the individual studies showed significant linkage with BMI: 3q22.1 (LOD 3.45, for the GENOA network black sample). Six additional regions were found with an associated LOD >2, including 3p24.1, 7p15.2, 7q22.3, 14q24.3, 16q12.2, and 17p11.2. Among these findings, the linkage at 7p15.2, 7q22.3, and 17p11.2 has been reported elsewhere. A modified Fisher's omnibus procedure was then used to combine the P values from each of the eight genome scans. A complimentary approach to the meta-analysis was undertaken, combining the average allele-sharing identity by descent (pi) for whites, blacks, and Mexican Americans. Using this approach, we found strong linkage evidence for a quantitative-trait locus at 3q27 (marker D3S2427; LOD 3.40, P=.03). The same location has been shown to be linked with obesity-related traits and diabetes in at least two other studies. These results (1) confirm the previously reported obesity-susceptibility locus on chromosomes 3, 7, and 17 and (2) demonstrate that combining samples from different studies can increase the power to detect common genes with a small-to-moderate effect, so long as the same gene has an effect in all samples considered.

Adult↗
PubMed2002

Association mapping, using a mixture model for complex traits.

Association mapping for complex diseases using unrelated individuals can be more powerful than family-based analysis in many settings. In addition, this approach has major practical advantages, including greater efficiency in sample recruitment. Association mapping may lead to false-positive findings, however, if population stratification is not properly considered. In this paper, we propose a method that makes it possible to infer the number of subpopulations by a mixture model, using a set of independent genetic markers and then testing the association between a genetic marker and a trait. The proposed method can be effectively applied in the analysis of both qualitative and quantitative traits. Extensive simulations demonstrate that the method is valid in the presence of a population structure.

Alleles↗
PubMed2002

Hypertension detection and control: population and policy implications.

The decline in cardiovascular diseases is by far the most remarkable achievement of medicine in the last half of the twentieth century. It can even be said that the treatment of hypertension is the only known medical intervention to have left a clear imprint on mortality trends. Much more remains to be accomplished, however, before even the majority of patients in the United States will be controlled with pharmacologic therapy [27,28]. Significant changes are needed to improve the practice of institutions, the adherence of physicians to appropriate guidelines, and the consistency of pill taking on the part of patients. Global risk evaluation is currently being used more widely in clinical practice to target therapy and improve its overall effectiveness; however, it is perhaps too early to assess its practical value. On theoretic grounds alone, much more needs to be done to refine prediction of cardiovascular risk as a clinical tool. Improvement in information technology, including an electronic medical record and on-line risk equations, will also be required before its full value can be realized.

Female↗
PubMed2002

Predicting incident diabetes in Jamaica: the role of anthropometry.

OBJECTIVE: To evaluate the performance of the body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in predicting incident diabetes in Jamaica. RESEARCH METHODS AND PROCEDURES: A cohort of 728 nondiabetic adults (290 men and 438 women), ages 25 to 74 years and residents of Spanish Town, Jamaica, were followed for a mean of 4 years. Participants had fasting and 2-hour postchallenge glucose concentrations measured at baseline and follow-up. RESULTS: There were 51 cases of incident diabetes (17 men and 34 women). All indices were independent predictors of diabetes, and none was clearly superior. The area under the receiver operating characteristics curves (95% confidence interval) for BMI was 0.74 (0.59 to 0.88) for men and 0.62 (0.51 to 0.72) for women. For waist circumference, these values were 0.78 (0.65 to 0.91) in men and 0.61 (0.50 to 0.71) in women. Similar results were obtained for WHR and WHTR. "Optimal" cut-off points for BMI were 24.8 kg/m(2) (men) and 29.3 kg/m(2) (women). For waist circumference, these were 88 cm and 84.5 cm for men and women, respectively. Corresponding values for WHR were 0.87 and 0.80 and for WHTR were 0.51 and 0.54, respectively. DISCUSSION: Cut-off points for waist circumference and WHR were similar to those proposed in developed countries for women but lower in men. Waist circumference could be useful in health promotion as an alternative to BMI.

Adult↗