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Biomedical subjects

S M Hofer

Publications and source records attributed to S M Hofer.

13 recordsLinked to original sources

Genetic and environmental influences on age at sexual initiation in the Colorado Adoption Project.

Whereas the majority of research on adolescent sexual initiation has focused solely on environmental factors, the present study used behavioral genetic analyses to investigate the relative contributions of genetic and environmental influences. Structural equation models were fitted to data from adoptive and non-adoptive sibling pairs (231 biologically related pairs and 169 unrelated pairs) from the Colorado Adoption Project. Information from censored individuals who had not yet experienced sexual initiation was maximized by adapting the twin survival analysis method of Pickles et al. (Behav Genet 24(5):457-468, 1994) to accommodate adoptive and non-adoptive siblings. Point estimates of variance components from an ACE model, including additive genetic (A), shared environmental (C), and non-shared environmental (E) influences were 28%, 24%, and 48%, respectively. Despite the lower point estimate for shared environmental effects than additive genetic effects, a CE model provided the best fit to the data. However, because adoptive siblings provide a direct estimate of shared environmental influences there is greater power to detect shared environmental effects in adoption designs. Evidence for genetic influences from our data were somewhat lower than those obtained in previous twin studies, possibly reflecting a return to more socially conservative sexual attitudes, changing sexual behaviors, or ambiguities in the wording of questions commonly used in research on adolescent sexuality.

Adolescent↗

Behavioral and psychological symptoms of dementia and caregivers' stress appraisals: intra-individual stability and change over short-term observations.

Dementia is commonly associated with memory loss, but Behavioral and Psychological Symptoms of Dementia (BPSD) such as disruptive behaviors, agitation, and problems with mood, usually have a more significant impact on caregivers' stress. It is known that BPSD and caregivers' stress reactions vary in frequency over the long-term course of dementia, however little is known about the variability over the short-term. The current study included 85 people with dementia and their primary caregivers assessed over three months. Caregivers used a 24-hour log on multiple, consecutive days to report behavioral symptoms of dementia on seven domains of behavior, as well as their stress reactions for each domain. Using latent growth curve analysis, most BPSD and caregiver stress appraisals were found to be, on average, stable over the three-month time frame. For many BPSD and stress appraisal models, however, intra-individual differences in rate of change were significantly different from the mean trend, indicating behaviors and stress are not stable over three months when assessed at the level of the individual. Covariates were used to explain individual differences in rates of change; however few variables were significantly associated with intra-individual short-term change over time.

Aged↗

Predictors of maternal child-feeding style: maternal and child characteristics.

We investigated relationships among maternal and child characteristics, and two aspects of maternal child-feeding styles that may place daughters at risk for developing problems with energy balance. Participants included 104 overweight (BMI> or =25) and 92 non-overweight (BMI<25) mothers and their 5-year-old, non-Hispanic, White daughters. Child-feeding styles included (a) restriction of daughters' intake of energy-dense snack food, and (b) pressure to eat more food. Predictors of child-feeding styles included measures of (1) maternal investment in weight and eating issues, including dietary restraint and weight concern, (2) child adiposity, (3) maternal perceptions of the child as underweight or overweight, and (4) maternal concern for child weight. Mothers reported using more restrictive feeding practices when they were invested in weight and eating issues, when they perceived daughters as overweight, when they were concerned about daughters' weight, and when daughters were heavier. Mothers reported using more pressure in child feeding when daughters were thinner, and when mothers perceived daughters as underweight. Further analyses examined whether relationships among child-feeding styles were different for overweight and non-overweight mothers. Overweight mothers' child-feeding styles appeared to be influenced by observable child weight characteristics, concerns for the child's weight status, and mothers' own history of overweight. Non-overweight mothers' child-feeding styles appeared to be influenced by distorted perceptions of and concerns for children, as well as distorted self-perceptions.

Adult↗

Age is no kinder to the better educated: absence of an association investigated using latent growth techniques in a community sample.

BACKGROUND: Higher education has been posited to protect against cognitive decline, either because the rate of decline is slower in the more highly educated or the start of decline is delayed. Latent growth models provide improved methodology to examine this issue. METHODS: The sample consisted of 887 participants aged 70-93 years in 1991 and followed up in 1994 and 1998. Latent growth models and standard regression techniques were used to examine the rate of cognitive decline in four cognitive measures while controlling for health status and sex. A delayed start model was examined by incorporating interaction effects in a regression model. RESULTS: Neither the latent growth models nor the regression techniques revealed a slower rate of decline for the more highly educated. The proportion of the highly educated showing no change was no larger than the proportion of the less well educated. There were no significant age by education interaction effects, no chronologically later accelerations in the rate of change as a function of education, and no differences in rate of decline between the first measurement interval and the second. CONCLUSIONS: Education may not protect against cognitive decline although it is associated with long-term individual differences in level of functioning. The discrepancy between our study and others may be attributable to attrition effects, follow-up length, sample age, scaling artefacts and negative publication bias. Most importantly, practice effects may favour the better educated and hence account for the supposed protective effect in many longitudinal studies of cognitive change.

Activities of Daily Living↗

Epistatic quantitative trait loci for alcohol preference in mice.

Alcohol consumption is a complex trait, responding to the influence of various genes and environmental influences acting in a quantitative fashion. Various studies in alcohol consumption processes have identified quantitative trait locus (QTL) regions across the mouse genome that appear to contribute to this phenotype. The purpose of this study was to examine the influence of interactions between alleles at different loci, a phenomenon known as epistasis, on previously identified QTLs for alcohol consumption in mice. A multiple regression model was developed and applied to test for the significance of the interaction between two QTLs and to quantify this interaction. Our results indicate the presence of epistasis between loci on mouse chromosomes 2 and 3 accounting for 7-8% of the variation in alcohol preference, respectively.

Alcohol Drinking↗

Origins of individual differences in episodic memory in the oldest-old: a population-based study of identical and same-sex fraternal twins aged 80 and older.

The relative importance of genetic and environmental influences on episodic memory in very late life was studied using a quantitative genetic approach. Identical (n = 125) and same-sex fraternal (n = 157) twin pairs, aged 80 and older (mean age = 83.3; SD = 3.1) and without a diagnosis of dementia were tested with seven memory measures: (1-2) Digit Span Forward and Backwards, (3) Prose Recall, (4) Thurstone's picture memory test, and the Memory in Reality (MIR) test, including the subtasks of (5) free recall, (6) recognition, and (7) relocation. Heritabilities, estimated by structural equation modeling, ranged from .04 to .49. The digit span backward test showed the highest heritability (h2 = .49), while heritabilities were typically lower for the long-term memory measures. The results demonstrate genetic influences on memory in the oldest-old, but suggest that the magnitude of these effects differs across memory measures.

Aged↗

Developmental loss of effect of a Chromosome 15 QTL on alcohol acceptance.

Human alcohol abuse and alcoholism have clear developmental features, suggesting the possibility of changes over time in heritability and in quantitative genetic architecture, and raising prospects of identifying individual genes or quantitative trait loci (QTLs) that display different influence on alcohol-related phenotypes at different ages. The identification of specific loci showing such age-related changes will open up opportunities of focused association studies and of genotype manipulation by various mating procedures. Most animal model research in alcohol assesses the phenotypes of the animals at an early age; developmental studies are rare. Here we report on a QTL on Chromosome (Chr) 15 of the mouse that has been shown in several populations, including BXD recombinant inbred strains, an F2, and genotypically selected lines, to affect a measure of alcohol consumption. In the present study, we measured alcohol acceptance in the genotypically selected animals and in an F4 sample at about 100 days and again at about 300 days of age. In both groups, and in both sexes, significant differences were observed at 100 days between animals that were homozygous for the "increasing" haplotype defining the QTL region and those homozygous for the "decreasing" haplotype. At 300 days of age, the effect is absent in females and has diminished or disappeared in males. The results provide a further confirmation of the Chr 15 QTL in young mice, offer a new perspective on the development of alcohol-related phenotypes, and have strong implications for research design.

Alcohol Drinking↗

A multivariate model for the analysis of sibship covariance structure using marker information and multiple quantitative traits.

A model was developed to detect effects of quantitative trait loci (QTLs) in sibships from simulated nuclear family data using the full covariance structure of the data and analyzing all five quantitative traits simultaneously in a multivariate model. Evidence of the presence of loci was detected on chromosomes 4, 8, 9, and 10. The method provided stable results and is worth further exploration for its performance and optimal sample size requirements under realistic conditions.

Alleles↗

Analysis of structure and discriminative power of the Mattis Dementia Rating Scale.

The study examines the factor structure and provides test of the discriminative properties of the 38-item Mattis Dementia Rating Scale (MDRS). The MDRS was designed a priori to measure five broad domains of cognitive abilities: attention, initiation/perseveration, conceptualization, construction, and memory. Complete item level data were collected at the USC Alzheimer Disease Research Center from 19 probable Alzheimer's Disease (AD) patients, 17 cases with dementia of various etiologies (e.g., multiple infarct), and 49 contrast subjects. Factor analyses, with rotation to equamax criterion, were performed on education partialled data. Five and six factor solutions accounted for most of the reliable variance and permitted simple structure theoretical description for separate subscales. These factors, similar to Mattis' design, can be characterized as Memory (Recall)/Verbal Fluency, Construction, Memory (short-term), Initiation/Perseveration, and Simple Commands. Cross-validated discriminant analyses performed on five unit-weighted composite variables derived from factor analysis provided better classification (72% vs 62%) than the 38 Mattis items alone.

Adult↗

Analysis with missing data in drug prevention research.

Missing data problems have been a thorn in the side of prevention researchers for years. Although some solutions for these problems have been available in the statistical literature, these solutions have not found their way into mainstream prevention research. This chapter is meant to serve as an introduction to the systematic application of the missing data analysis solutions presented recently by Little and Rubin (1987) and others. The chapter does not describe a complete strategy, but it is relevant for (1) missing data analysis with continuous (but not categorical) data, (2) data that are reasonably normally distributed, and (3) solutions for missing data problems for analyses related to the general linear model in particular, analyses that use (or can use) a covariance matrix as input. The examples in the chapter come from drug prevention research. The chapter discusses (1) the problem of wanting to ask respondents more questions than most individuals can answer; (2) the problem of attrition and some solutions; and (3) the problem of special measurement procedures that are too expensive or time consuming to obtain for all subjects. The authors end with several conclusions: Whenever possible, researchers should use the Expectation-Maximization (EM) algorithm (or other maximum likelihood procedure, including the multiple-group structural equation-modeling procedure or, where appropriate, multiple imputation, for analyses involving missing data [the chapter provides concrete examples]); If researchers must use other analyses, they should keep in mind that these others produce biased results and should not be relied upon for final analyses; When data are missing, the appropriate missing data analysis procedures do not generate something out of nothing but do make the most out of the data available; When data are missing, researchers should work hard (especially when planning a study) to find the cause of missingness and include the cause in the analysis models; and Researchers should sample the cases originally missing (whenever possible) and adjust EM algorithm parameter estimates accordingly.

Algorithms↗

Genes as gerontological variables: uniform genotypes.

Genetic conceptualizations and procedures have become integral to the conduct of research across the spectrum of life sciences, including gerontology, even when genetics is not the focus of inquiry. Among the research tools thus provided, one of the most basic is that of inbred strains. A close approximation to genetic uniformity is achieved by a sufficient number of successive generations of matings of relatives, and, once this near-uniformity is attained, the members of an inbred strain constitute a reference group relatively stable over time and available to diverse investigators. Different inbred strains possess different genotypes, so that numerous distinctive reference groups are available. The stability of these groups enhances prospects of replication-testing, and makes possible the focused accumulation of pertinent data. Phenotypic differences among strains identify particular groups that can be most appropriate for particular subsequent research objectives (and also provide ipso facto evidence of genetic influence on the phenotype). The very substantial advantages of the uniform genotypes provided by inbred strains (and by their F1 offspring) are purchased at the cost of limited generalizability of results and constraints on assessment of co-variation among variables. Uniform genotypes are, thus, not a tool for all purposes but must be seen as a powerful basic tool within an abundant genetic tool-kit. Particular research purposes will require use of more than one tool from the kit.

Aging↗

Genes as gerontological variables: genetically heterogeneous stocks and complex systems.

In gerontological research utilizing animal models, a major general strategy has been the use of uniform genotypes of inbred strains or their F1 hybrids. These animal models provide standard reference groups that are of major importance in establishing a reliable data base on aging phenomena. There are limitations to their usage, however, particularly in respect to descriptions or evaluations of variances or of covariance relationships. For these purposes, genetically heterogeneous stocks have the advantage that phenotypic variance (and covariance) has a genetic as well as an environmental component. The advantages of genetic heterogeneity are best realized when the stock has been systematically derived (usually by intercrossing of inbred strains) and maintained by a mating scheme of sufficient size to minimize inbreeding. Genetically heterogeneous stocks are of particularly high potential value in the study of complex systems. Some examples of their use in a gerontological context are provided.

Aging↗

Understanding Ageing. An evaluation of research designs for assessing the interdependence of ageing-related changes.

BACKGROUND: Cross-sectional studies of samples varying widely in age have found moderate to high levels of shared age-related variance among measures of cognitive and physiological capabilities, leading researchers to posit common factors or common causal influences for diverse age-related phenomenon. OBJECTIVE: The influence of population average changes with age on cross-sectional estimates of association has not been widely appreciated in developmental and ageing research. Covariances among age-related variables in cross-sectional studies are highly confounded in regards to inferences about associations among rates of change within individuals since covariances can result from a number of sources including average population age-related differences (fixed age effects) in addition to initial individual differences and individual differences in rates of ageing (random age effects). Analysis of narrow age-cohort samples may provide a superior analytical basis for testing hypotheses regarding associations between rates of change in cross-sectional studies. CONCLUSIONS: The use of age-heterogeneous cross-sectional designs for evaluating interdependence of ageing-related processes is discouraged since associations will not necessarily reflect individual-level correlated rates of change. Typical cross-sectional studies do not provide sufficient evidence for the interdependence of ageing-related changes and should not serve as the basis for theories and hypotheses of ageing. Reanalyzing existing cross-sectional studies using a sequential narrow-age cohort approach provides a useful alternative for evaluating associations between ageing-related changes. Longitudinal designs, however, provide a much stronger basis for inference regarding associations between rates of ageing within individuals.

Adult↗