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Biomedical subjects

J H Moore

Publications and source records attributed to J H Moore.

At least 19 recordsLinked to original sources
PubMed2006

Gender-specific correlations of plasminogen activator inhibitor-1 and tissue plasminogen activator levels with cardiovascular disease-related traits.

BACKGROUND: The purpose of this study was to examine the correlations between plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) and cardiovascular disease-related traits in a general population and whether these correlations differed between females and males. METHODS: Plasma PAI-1 and t-PA antigen levels and C-reactive protein (CRP), HDL-cholesterol, triglycerides, total cholesterol, systolic blood pressure, diastolic blood pressure, urinary albumin excretion, and glucose were measured in the population-based PREVEND study in Groningen, the Netherlands (n = 2527). RESULTS: Except for CRP and total cholesterol levels, all traits were significantly different between gender (P < 0.001). PAI-1 levels were correlated with all measured cardiovascular disease-related traits (P < 0.01) in both females and males. Except for urinary albumin excretion, similar results, albeit less significant, were found for t-PA levels. Age-adjusted correlations between PAI-1 and CRP, triglycerides, total cholesterol, systolic blood pressure, and diastolic blood pressure differed significantly between females and males (P < 0.01). Many of the gender differences were predominantly present between premenopausal females and males. CONCLUSION: PAI-1 and t-PA levels were correlated with cardiovascular disease-related traits in subjects obtained from the general population and several of these correlations differed across gender. The correlations found in the present study suggest the presence of coordinated patterns of cardiovascular risk factors and indicate which traits might influence PAI-1 and t-PA levels and thereby provide a framework and potential tool for therapeutic intervention to reduce thromboembolic events in the general population.

Adult↗
PubMed2006

Hybrid grammar-based approach to nonlinear dynamical system identification from biological time series.

We introduce a grammar-based hybrid approach to reverse engineering nonlinear ordinary differential equation models from observed time series. This hybrid approach combines a genetic algorithm to search the space of model architectures with a Kalman filter to estimate the model parameters. Domain-specific knowledge is used in a context-free grammar to restrict the search space for the functional form of the target model. We find that the hybrid approach outperforms a pure evolutionary algorithm method, and we observe features in the evolution of the dynamical models that correspond with the emergence of favorable model components. We apply the hybrid method to both artificially generated time series and experimentally observed protein levels from subjects who received the smallpox vaccine. From the observed data, we infer a cytokine protein interaction network for an individual's response to the smallpox vaccine.

Algorithms↗
PubMed2006

A novel method to identify gene-gene effects in nuclear families: the MDR-PDT.

It is now well recognized that gene-gene and gene-environment interactions are important in complex diseases, and statistical methods to detect interactions are becoming widespread. Traditional parametric approaches are limited in their ability to detect high-order interactions and handle sparse data, and standard stepwise procedures may miss interactions that occur in the absence of detectable main effects. To address these limitations, the multifactor dimensionality reduction (MDR) method [Ritchie et al., 2001: Am J Hum Genet 69:138-147] was developed. The MDR is well-suited for examining high-order interactions and detecting interactions without main effects. The MDR was originally designed to analyze balanced case-control data. The analysis can use family data, but requires a single matched pair be selected from each family. This may be a discordant sib pair, or may be constructed from triad data when parents are available. To take advantage of additional affected and unaffected siblings requires a test statistic that measures the association of genotype with disease in general nuclear families. We have developed a novel test, the MDR-PDT, by merging the MDR method with the genotype-Pedigree Disequilibrium Test (geno-PDT)[Martin et al., 2003: Genet Epidemiol 25:203-213]. MDR-PDT allows identification of single-locus effects or joint effects of multiple loci in families of diverse structure. We present simulations to demonstrate the validity of the test and evaluate its power. To examine its applicability to real data, we applied the MDR-PDT to data from candidate genes for Alzheimer disease (AD) in a large family dataset. These results show the utility of the MDR-PDT for understanding the genetics of complex diseases.

Algorithms↗
PubMed2005

Analysis of the RELN gene as a genetic risk factor for autism.

Several genome-wide screens have indicated the presence of an autism susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at 7q22 within this region is the candidate gene reelin (RELN). RELN encodes a signaling protein that plays a pivotal role in the migration of several neuronal cell types and in the development of neural connections. Given these neurodevelopmental functions, recent reports that RELN influences genetic risk for autism are of significant interest. The total data set consists of 218 Caucasian families collected by our group, 85 Caucasian families collected by AGRE, and 68 Caucasian families collected at Tufts University were tested for genetic association of RELN variants to autism. Markers included five single-nucleotide polymorphisms (SNPs) and a repeat in the 5'-untranslated region (5'-UTR). Tests for association in Duke and AGRE families were also performed on four additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Family-based association analyses (PDT, Geno-PDT, and FBAT) were used to test for association of single-locus markers and multilocus haplotypes with autism. The most significant association identified from this combined data set was for the 5'-UTR repeat (PDT P-value=0.002). These analyses show the potential of RELN as an important contributor to genetic risk in autism.

5' Untranslated Regions↗
PubMed2004

Practical means for the study of electron correlation in atoms.

Electron correlation is basic to the understanding of a diverse range of physical and chemical phenomena, yet, there have been no direct measurements of the correlated motion of electrons. Measurement of the correlated momenta of atomic electrons is possible via electron-impact double ionization provided that the ionizing collisions are both impulsive and binary, and the three-body scattering mechanism is known. The results reported here satisfy these conditions, and a practical means for the study of atomic electron correlation through measurement of two-electron momentum densities is presented.

Journal Article↗
PubMed2004

Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is a complex genetic disease, which results from interactions between multiple genes and environmental factors without any single factor having strong independent effects. This study was done to identify gene to gene interactions which could be associated with the risk of Type 2 diabetes. METHODS: We genotyped 23 different loci in the 15 candidate genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non-diabetic control subjects. We analysed gene to gene interactions among 23 polymorphic loci using the multifactor-dimensionality reduction (MDR) method, which has been shown to be effective for detecting and characterising gene to gene interactions in case-control studies with relatively small samples. RESULTS: The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma ( PPARgamma) gene. This interaction showed the maximum consistency and minimum prediction error among all gene to gene interaction models evaluated. Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016). CONCLUSIONS/INTERPRETATION: Using the MDR method, we showed a two-locus interaction between the UCP2 and PPARgamma genes among 23 loci in the candidate genes of Type 2 diabetes. The determination of such genotype combinations contributing to Type 2 diabetes mellitus could provide a new tool for identifying high-risk individuals.

Aged↗
PubMed2002

The relationship between plasma t-PA and PAI-1 levels is dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms.

Thrombus formation and degradation is partly due to a complex interplay between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). There is accumulating evidence that plasma levels of t-PA and PAI-1 may be influenced by an interaction between the fibrinolytic and renin-angiotensin systems. The goal of this study was to conduct an exploratory data analysis to determine whether there is evidence that the relationship (i.e. correlation) between plasma t-PA and PAI-1 is influenced by interactive effects of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) and plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphisms in a sample of 50 unrelated African Americans and 117 unrelated Caucasians. In a single-locus analysis, no evidence for heterogeneity of plasma t-PA and PAI-1 correlations among either ACE I/D or PAI-1 4G/5G genotypes was detected. However, using the combinatorial partitioning method for exploratory data analysis, we identified evidence that is suggestive of heterogeneity of plasma t-PA and PAI-1 correlations among multilocus ACE I/D and PAI-1 4G/5G genotypes in African American females, Caucasian females, Caucasian males, but not African American males. From these results, we propose as a working hypothesis that the correlation between plasma t-PA and PAI-1 may be dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms. This study supports the idea that interactions between the fibrinolytic and renin-angiotensin systems play an important role in the genetic architecture of plasma t-PA and PAI-1.

Adult↗
PubMed2002

A comparison of combinatorial partitioning and linear regression for the detection of epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms on plasma PAI-1 levels.

The detection and characterization of epistasis or non-additive gene-gene interactions remains a statistical challenge in genetic epidemiology. The recently developed combinatorial partitioning method (CPM) may overcome some of the limitations of linear regression for the exploratory analysis of non-additive epistatic effects. The goal of this study was to compare CPM with linear regression analysis for the exploratory analysis of non-additive interactive effects of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) and plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphisms on plasma PAI-1 levels in a sample of 50 unrelated African Americans and 117 unrelated Caucasians. Using linear regression, we documented the additive effects of the ACE and PAI-1 genes on plasma PAI-1 levels in African American females (R(2) = 0.10), African American males (R(2) = 0.16), Caucasian females (R(2) = 0.11), and Caucasian males (R2 = 0.09). Using CPM, we found evidence for non-additive effects of the ACE and PAI-1 genes in both African American females (R(2) = 0.22) and African American males (R(2) = 0.24) but not in Caucasian females (R(2) = 0.10) or Caucasian males (R(2) = 0.11). The results of this exploratory data analysis support previous experimental, clinical, and epidemiological studies that have proposed as a working hypothesis that the ACE gene mediates interaction effects of the fibrinolytic and renin-angiotensin systems on plasma levels of PAI-1.

Black People↗
PubMed2001

Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer.

One of the greatest challenges facing human geneticists is the identification and characterization of susceptibility genes for common complex multifactorial human diseases. This challenge is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes and with environmental exposures. We introduce multifactor-dimensionality reduction (MDR) as a method for reducing the dimensionality of multilocus information, to improve the identification of polymorphism combinations associated with disease risk. The MDR method is nonparametric (i.e., no hypothesis about the value of a statistical parameter is made), is model-free (i.e., it assumes no particular inheritance model), and is directly applicable to case-control and discordant-sib-pair studies. Using simulated case-control data, we demonstrate that MDR has reasonable power to identify interactions among two or more loci in relatively small samples. When it was applied to a sporadic breast cancer case-control data set, in the absence of any statistically significant independent main effects, MDR identified a statistically significant high-order interaction among four polymorphisms from three different estrogen-metabolism genes. To our knowledge, this is the first report of a four-locus interaction associated with a common complex multifactorial disease.

Alleles↗
PubMed2001

Improved power of sib-pair linkage analysis using measures of complex trait dynamics.

The influence of epistasis on a quantitative trait can reduce the power of linkage analysis to identify the underlying loci. In the present study, we simulated a complex trait derived from a dynamic one-locus gene expression system with epistasis arising from feedback regulation and tested the power of sib-pair linkage analysis methods for detecting the underlying quantitative trait locus (QTL). Using this simple genetic architecture, we demonstrate that the power of sib-pair linkage analysis can be greatly improved if measures of complex trait dynamics are considered.

Computer Simulation↗
PubMed2001

Flexural wave propagation velocity and bone mineral density in females with and without tibial bone stress injuries.

STUDY DESIGN: Case-control nonexperimental design. OBJECTIVES: To compare flexural wave propagation velocity (FWPV) and tibial bone mineral density (BMD) in women with and without tibial bone stress injuries (BSIs). BACKGROUND: Physical therapists, particularly in military and sports medicine settings, routinely diagnose and manage stress fractures or bone stress injuries. Improved methods of preparticipation quantification of tibial strength may provide markers of BSI risk and thus potentially reduce morbidity. METHODS AND MEASURES: Bone mineral density, FWPV, bone geometry, and historical variables were collected from 14 subjects diagnosed with tibial BSIs and 14 age-matched controls; all 28 were undergoing military training. RESULTS: No difference was found between groups in FWPV and tibial BMD when analyzed with t tests (post hoc power = 0.89 and 0.81, respectively). Furthermore, no difference was found in tibial length, tibial width, femoral neck BMD, and lumbar spine BMD among the groups. There were no differences between the 2 groups in smoking history, birth control pill use, and onset of menarche. Finally, sensitivity and positive likelihood ratios for FWPV (0.14 and 0.63), tibial BMD (0.0 and 0.0), and lumbar BMD (0.18 and 2.0) were low, while specificity was high (0.77, 0.93, and 0.91, respectively). CONCLUSION: Current bone analysis devices and methods may not be sensitive enough to detect differences in tibial material and structure; local stresses on bone may be more important in the development of BSIs than the overall structural stiffness.

Absorptiometry, Photon↗
PubMed2001

Test-retest reliability of the ulnar F-wave minimum latency versus ulnar distal motor latency in healthy adults.

BACKGROUND AND PURPOSE: The purposes of this study were to explore reliability of the ulnar F-wave minimum latency (Fmin) and the ulnar distal motor latency (DML) and to contrast those levels of reliability in order to reveal whether physiologic lability is the primary contributor to unwanted variability in Fmin measurements. SUBJECTS AND METHODS: Fmin and DML in the Abductor Digiti Minimi muscle were measured bilaterally by two raters in 50 healthy adults (n = 100 hands, 70 male, 30 female) with 3-14 days between testing sessions. RESULTS: Intrarater reliability (ICC 3,1) for the Fmin was 0.89 with a standard error of the measurement (SEM) of 0.77 msec. Interrater reliability (ICC 2,1) for the Fmin was 0.80 with a SEM of 1.04 msec. Intrarater reliability (ICC 3,1) for the DML was 0.71 with a SEM of 0.18 msec. Interrater reliability (ICC 2,1) for the DML was 0.76 with a SEM of 0.19 msec. DISCUSSION AND CONCLUSIONS: Contrary to our hypothesis, the Fmin had a higher reliability than the DML. The DML did not display the high reliability other investigators have reported. We conclude the Fmin is a reliable measurement when 10 supramaximal stimulations are administered to healthy, young to middle-aged adult subjects. However, no inferences were made regarding relative levels of psychologic lability for the two latencies.

Adult↗
PubMed2000

Detection of linear and nonlinear dependencies in time series using the method of surrogate data in S-PLUS.

A general implementation of the method of surrogate data in the S programming language for use with the S-PLUS statistical package is presented. We illustrate the application of the S functions to testing hypotheses about a human heart rate time series and demonstrate that there is evidence for both linear and nonlinear dependencies. We expect these S functions will be useful for the application of the method of surrogate data to the analysis of biomedical time series using the S-PLUS statistical software package.

Data Interpretation, Statistical↗
PubMed2000

Effect of time of day on intraindividual variability in ambulatory blood pressure.

The aim of this study was to determine whether intraindividual blood pressure (BP) variability, measured by noninvasive ambulatory monitoring, differs between the active (daytime) and inactive (nighttime) periods of the day. We obtained ambulatory BP recordings in 143 healthy adults (95 men, 48 women) from Rochester, Minnesota. Readings were obtained every 10 min for a 24-h period. We calculated the standard deviation of each individual's BP readings about the means for the active period and for the inactive period as measures of intraindividual BP variability. In men, mean within-individual standard deviations for both systolic (SBP) and diastolic blood pressure (DBP) were significantly greater during the inactive period than during the active period (for SBP: 10.3 +/- 2.1 v 11.9 +/- 2.7, P < .0001; for DBP: 8.8 +/- 2.0 v 9.7 +/- 2.5, P = .0027). In women, the mean within-individual standard deviation for SBP did not differ significantly between the active and inactive periods (9.7 +/- 2.2 v 10.3 +/- 2.4, P = 0.225) but for DBP was significantly greater during the inactive period than during the active period (8.1 +/- 2.0 v 9.2 +/- 2.3, P = .020). Statistically significant predictors of intraindividual BP variability included measures of age and body size, metabolic traits, neuroendocrine traits, erythrocyte cation traits, and renal function traits. This study demonstrates that intraindividual BP variability, as measured by noninvasive ambulatory monitoring, is as great or greater during the inactive period as during the active period of the day.

Adult↗
PubMed2000

Predictors of interindividual variation in ambulatory blood pressure and their time or activity dependence.

The objectives of this study were to determine whether total interindividual variation in blood pressure (BP) differs between inactive and active hours of the day, to identify predictors of interindividual variation in BP, and to assess whether variation associated with any of these identified predictors is greater (or less) during inactive hours than during active hours of the day. We obtained ambulatory BP recordings over 20 consecutive hours (12 active, out of bed [daytime]; and 8 inactive, in bed [nighttime]) in a sample of 240 unrelated, non-Hispanic white adults (138 men; 102 women). We estimated total interindividual variation in BP, and the percentage of interindividual variation associated with measures of age and body size, metabolic traits, catecholamines, erythrocyte cation transport, and renal function. We used linear regression to assess changes in the hourly estimates of total interindividual variation and in variation attributable to each set of predictor traits over the 20 h. In both men and women, total interindividual variation in systolic BP was significantly greater (not less) during inactive hours than during active hours. In addition, in women, total interindividual variation in diastolic BP was as great during inactive hours as during active hours. Each set of traits considered predicted a statistically significant percentage of interindividual variation in BP. None of the sets of traits predicted a greater percentage of interindividual variation during the inactive hours than during the active hours. Measures of age and body size, catecholamines, cation transport and renal function traits predicted significantly less interindividual variation during inactive hours than during active hours of the day. That total interindividual variation in BP is as great or greater during inactive hours than during active hours of the day emphasizes the potential for differences in nighttime BP to contribute to the development of cardiovascular disease. In as much as the predictors of interindividual variation in BP differ between the daytime and nighttime, the causes of variation during these two times may also differ.

Adult↗
PubMed1999

Test-retest reliability of the ulnar F-wave minimum latency in normal adults.

BACKGROUND AND PURPOSE: The purpose of this study was to measure the test-retest reliability of the ulnar F-wave minimum latency (Fmin) in normal adults. A reliable Fmin measure allows clinicians to ascribe changes in latency to true changes in a subject and not merely random daily variation. SUBJECTS AND METHODS: Fmin in the Abductor Digiti Minimi muscle was measured bilaterally in 49 healthy adults (n = 98) with a three day separation between tests. RESULTS: The Fmin reliability estimate as measured by intraclass correlation coefficient (3,1) was 0.59 with a standard error of measurement (SEM) of 1.3 msec. A paired t-test showed no significant difference (t = 1.7, df = 97, p > 0.05) between the mean scores from the two testing sessions. DISCUSSION AND CONCLUSIONS: We found moderate reliability and relatively low precision (high SEM) in Fmin scores taken from healthy individuals on two separate days. Strict adherence to our protocol and an acceptable overall precision of measurements (as measured by mean scores) suggest the contributions of rater and instrument error were low in our study. We conclude that 1) valid clinical interpretation of minimum F-wave latency findings is questionable because the Fmin measurement appears to have only moderate reliability, and 2) the lability of the phenomenon itself is the most likely contributor to variability in the Fmin latencies. Further research is warranted before electrophysiologists may be justified in attributing small changes in the Fmin to actual changes in the subject.

Action Potentials↗