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Biomedical subjects

L R Cardon

Publications and source records attributed to L R Cardon.

62 records · Page 4Linked to original sources

Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments?

We investigated the mediating role of genetic factors in the clustering of hypertension, diabetes, and obesity, using the twin registry maintained by the National Academy of Sciences--National Research Council. The study sample included 2,508 male twin pairs born between 1917 and 1927 who responded to a mailed questionnaire that covered demographic variables, cardiovascular risk factors, and health behaviors. The incidence of hypertension and diabetes in this cohort was ascertained from subjects' self-report of a physician diagnosis and/or the use of prescription medications. The body-mass index calculated from self-reports of height and weight was used as a measure of obesity. Descriptive analyses indicated probandwise concordance rates of 34.0%, 31.2%, and 32.7%, respectively, for the joint occurrences of hypertension and diabetes, hypertension and obesity, and diabetes and obesity in MZ twin pairs. Corresponding concordance rates in DZ twin pairs were 8.1%, 14.9%, and 2.8%. The probandwise concordance for the clustering of all three conditions in the same individuals was 31.6% in MZ pairs and 6.3% in DZ pairs (relative risk 5.0; X2(1) = 2.6; P < .15). Multivariate genetic modeling of the correlation in liabilities to develop these conditions suggested the presence of a common latent factor mediating the clustering of hypertension, diabetes, and obesity in this twin sample. This common factor was influenced by both genetic and environmental effects (59% 8 genetic, 41% environmental). The genetic influences on the common latent factor were due to dominant rather than additive sources; the environmental influences appeared to be specific rather than shared by co-twins.

Aged↗

A sib-pair approach to interval mapping of quantitative trait loci.

An interval mapping procedure based on the sib-pair method of Haseman and Elston is developed, and simulation studies are carried out to explore its properties. The procedure is analogous to other interval mapping procedures used with experimental material, such as plants and animals, and yields very similar results in terms of the location and effect size of a quantitative trait locus (QTL). The procedure offers an advantage over the conventional Haseman and Elston approach, in terms of power, and provides useful information concerning the location of a QTL. Because of its simplicity, the method readily lends itself to the analysis of selected samples for increased power and the evaluation of multilocus models of complex phenotypes.

Alleles↗

Comparative DNA sequence features in two long Escherichia coli contigs.

The recent sequencing of two relatively long (approximately 100 kb) contigs of E.coli presents unique opportunities for investigating heterogeneity and genomic organization of the E.coli chromosome. We have evaluated a number of common and contrasting sequence features in the two new contigs with comparisons to all available E.coli sequences (> 1.6 Mb). Our analyses include assessments of: (i) counts and distributions of restriction sites, special oligonucleotides (e.g., Chi sites, Dam and Dcm methylase targets), and other marker arrays; (ii) significant distant and close direct and inverted repeat sequences; (iii) sequence similarities between the long contigs and other E.coli sequences; (iv) characterization and identification of rare and frequent oligonucleotides; (v) compositional biases in short oligonucleotides; and (vi) position-dependent fluctuations in sequence composition. The two contigs reveal a number of distinctive features, including: a cluster of five repeat/dyad elements with very regular spacings resembling a transcription attenuator in one of the contigs; REP elements, ERICs, and other long repeats; distinction of the Chi sequence as the most frequent oligonucleotide; regions of clustering, overdispersion, and regularity of certain restriction sites and short palindromes; and comparative domains of inhomogeneities in the two long contigs. These and other features are discussed in relation to the organization of the E.coli chromosome.

Base Sequence↗

A genetic and environmental time series analysis of blood pressure in male twins.

Systolic and diastolic blood pressures were measured on 254 monozygotic (MZ) and 260 dizygotic (DZ) male twin pairs, during middle age (average age 48 years) and at two later age points. Genetic and environmental components of covariation were modeled by time series. For both measures, shared environmental influences were absent and specific environmental influences were largely time-specific. Although heritability was about 0.5 at each time point, genetic variation present at middle age contributed only about 60% to that present 9 years later, the remaining 40% being new. Fifteen years later, at the third time point, no new genetic variation was evident, variation in individual differences being entirely attributable to genetic differences laid down at the two earlier ages.

Blood Pressure↗

Expectation maximization algorithm for identifying protein-binding sites with variable lengths from unaligned DNA fragments.

An Expectation Maximization algorithm for identification of DNA binding sites is presented. The approach predicts the location of binding regions while allowing variable length spacers within the sites. In addition to predicting the most likely spacer length for a set of DNA fragments, the method identifies individual sites that differ in spacer size. No alignment of DNA sequences is necessary. The method is illustrated by application to 231 Escherichia coli DNA fragments known to contain promoters with variable spacings between their consensus regions. Maximum-likelihood tests of the differences between the spacing classes indicate that the consensus regions of the spacing classes are not distinct. Further tests suggest that several positions within the spacing region may contribute to promoter specificity.

Algorithms↗

Differential heritability across levels of cognitive ability.

Differences in heritability and shared environmentality across levels of cognitive ability were assessed in a sample of 264 twin pairs tested at 1 year of age and in subsets tested at 2 and 3 years. Using an extension of the DF multiple regression methodology for analyzing twin data, no evidence was found for a linear or quadratic effect of level of cognitive ability on estimates of heritability or shared environmentality.

Aptitude↗

A LISREL 8 model with constrained parameters for twin and adoptive families.

Constrained optimization recently has been implemented in the LISREL software package, allowing formulation of parent-offspring transmission models in a simple and efficient manner. A reverse path model of parental transmission is described within the LISREL framework for application to twin and/or adoptive family data. The model incorporates genetic and environmental parameter constraints arising from assortative mating and cultural transmission. An illustration of the LISREL model is given using measures obtained from twins and parents involving fear of social criticism.

Adoption↗

A sib-pair regression model of linkage disequilibrium for quantitative traits.

A multiple-regression model is described for the detection of linkage disequilibrium in quantitative trait loci. The model is developed for application to large numbers of single nucleotide polymorphism (SNP) markers genotyped on small nuclear families. Parental data are not required by the method, although it provides a direct means to test quantitative trait locus-marker allele association and to determine whether any such association is attributable to linkage disequilibrium or population admixture. Analytical expectations for the regression coefficients are derived, allowing direct interpretation of the parameter estimates. Simulation studies indicate a substantial improvement in power over classical linkage studies of sibling pairs and show the effects of population admixture on the model outcomes.

Humans↗