Biomedical subjects

M C Neale

Publications and source records attributed to M C Neale.

At least 145 records · Page 8Linked to original sources

PubMed1992

The relationship between age at first drug use and teenage drug use liability.

Our analyses of Carey's (1992) simulated data set of substance abuse in a cohort of adolescent twins were aimed at answering the question What is the relationship between age at first drug use and EVER having used drugs (i.e., teenage drug use liability)? Three analytic methods were used to determine whether age at first drug use was (1) a "perfect" index of drug use liability, (2) correlated in relatives but conditionally independent of drug use liability, or (3) causally influenced by drug use liability and by factors independent of liability. The analytic methods included nonmetric multidimensional scaling, multifactorial threshold model-fitting to contingency tables, and pedigree-based likelihood formulations for the raw data. All approaches indicated that age at first drug use was a perfect index of drug use liability. Further, model-fitting results indicated that only shared environmental factors accounted for twin similarity in the onset and timing of drug use. We discuss the limitations of each of the analytic methods and integrate our findings with the true model used in Carey's simulation.

Adolescent↗

PubMed1992

Genetic and environmental factors in the aetiology of menstrual, premenstrual and neurotic symptoms: a population-based twin study.

Symptoms during the premenstrual and menstrual phases of the female reproductive cycle were assessed in 827 pairs of female same-sex twins from a population-based registry. By conventional factor analysis, premenstrual and menstrual symptoms were relatively independent of one another and of baseline 'neurotic' symptoms (i.e. anxiety, depression and somatization). Familial resemblance for menstrual and premenstrual symptoms was due solely to genetic factors with heritability estimates of 39.2% and 35.1%, respectively. Multivariate genetic analysis revealed distinct genetic and environmental factors for menstrual, premenstrual and neurotic symptoms. The genes and individual-specific experiences that predispose to premenstrual symptoms appear to be largely distinct from those which predispose either to menstrual or to neurotic symptoms. The generalizability of these results may be limited because only a modest number of premenstrual and menstrual symptoms were assessed, all by retrospective self-report.

Adult↗

PubMed1992

Bulimia nervosa and major depression: a study of common genetic and environmental factors.

A genetic analysis of the co-occurrence of bulimia and major depression (MD) was performed on 1033 female twin pairs obtained from a population based register. Personal interviews were conducted and clinical diagnoses made according to DSM-III-R criteria. Additive genes, but not family environment, are found to play an important aetiological role in both bulimia and MD. The genetic liabilities of the two disorders are correlated 0.456. While unique environmental factors account for around half of the variation in liability to both bulimia and MD, these risk factors appear to be unrelated, i.e., each disorder has its own set of unique environmental risk factors. Thus, the genetic liability of bulimia and MD is neither highly specific nor entirely non-specific. There is some genetic correlation between the two disorders as well as some genetic and environmental risk factors unique to each disorder. Limitations and directions for future research are discussed.

Adolescent↗

PubMed1992

Social support, depressed mood, and adjustment to stress: a genetic epidemiologic investigation.

A survey of 821 same-sex female twin pairs from a population-based registry assessed 8 dimensions of social support and social integration. Twin analyses documented significant common environmental influences on 5 of these 8 measures and significant genetic influences on 5 of the 8. A decomposition of the multiplicative association between support and a measure of stressful life experiences in predicting depressed mood--an association typically interpreted as providing evidence for a stress-buffering effect of social support--shows clearly that it is the environmental and genetic factors that cause support, rather than support itself, that buffer the effects of stress on mood in most cases. We discuss the implications of this result for future research on the relationship between social support and psychopathology.

Adaptation, Psychological↗

PubMed1992

Evidence for genetic influences on personality from self-reports and informant ratings.

Self-report data on Extraversion (E) and Neuroticism (N), together with ratings by the co-twin, were obtained from a sample of 826 adult female twin pairs ascertained through a population-based twin register. Data were analyzed using a model that allowed for the contributions to personality ratings of the rater's personality (rater bias) as well as of the personality of the person being rated. For E, but not for N, significant rater bias was found, with extraverted respondents tending to underestimate, and introverted respondents tending to overestimate, the Extraversion of their co-twins. Good agreement between self-reports and ratings by the respondent's co-twin was found for both E and N. Substantial genetic influences were found for both personality traits, confirming findings from genetic studies of personality that have relief only on self-reports of respondents.

Adult↗

PubMed1992

Familial influences on the clinical characteristics of major depression: a twin study.

We sought in this study to clarify the role that familial factors play in influencing the clinical presentation of major depression (MD). We examined the similarity of the historical and symptomatic features of MD in 176 pairs of female-female monozygotic (MZ) and dizygotic (DZ) twins from a population-based registry, where both members reported a history of MD defined by DSM-III-R criteria. The age at onset and treatment-seeking were significantly correlated in all twin pairs and the correlation in concordant DZ pairs was actually somewhat higher than in concordant MZ twins. The degree of impairment was modestly correlated in all twin pairs with substantially higher correlations in MZ vs DZ twins. No twin resemblance was observed for number of episodes or longest duration of an episode. Twin resemblance for the clinical features of MD was modest, but so was their consistency for the same individual over successive 1-year periods. However, in 5 of the 6 neurovegetative symptoms involving changes in appetite, weight and sleep, MZ twins were significantly correlated and correlations were significantly greater in concordant MZ vs DZ twins. Although the familial factors that cause twin resemblance for the age at onset and treatment seeking appear to be largely environmental, twin resemblance for the degree of impairment and neurovegetative symptoms are probably due largely to genetic factors. Our results suggest that familial factors influence the predisposition to some clinical features of MD.

Adult↗

PubMed1992

Aphidicolin-inducible common fragile-site expression: results from a population survey of twins.

Common chromosomal fragile sites appear to be ubiquitous in humans and other mammals, and, although the molecular basis and function of these sites remain an enigma, it has been speculated that they may be a cytogenetic expression of gene activity. A population survey of 28 twin pairs was conducted to assess the heritability of common fragile-site expression. Our data yielded a heritability estimate of .88 for total site expression, suggesting that these sites may result from some common process that is under relatively stringent genetic control. An analysis of the expression of individual autosomal sites revealed that expression on both homologues in the same cell occurred more frequently than expected.

Adolescent↗

PubMed1991

A model for comparative ratings in studies of within-family differences.

Comparative ratings between pairs of siblings or other relatives are commonly used to refine measures of intrafamily variation. A simple model, based on signal detection theory, is proposed which shows how comparative ratings can be used to estimate within-pair variances of true scores, which can, in turn, be modeled with any of the conventional approaches to partitioning genetic and environmental variance within families.

Humans↗

PubMed1991

Coping: a genetic epidemiological investigation.

This study examines data on self-report coping behaviour, life events and symptoms of anxiety and depression in a general population sample of 827 female twin pairs. Factor analysis identified three almost uncorrelated coping factors: turning to others; problem solving; and denial. Turning to others and problem solving were negatively and denial was positively related to levels of anxiety and depression. Turning to others and problem solving buffered the depressogenic and anxiogenic effects of stressful life events, while denial exacerbated the anxiogenic effects of life events. Structural equation model-fitting indicated that twin resemblance in turning to others and problem solving could be explained entirely by genetic factors with an estimated heritability of 30 and 31%, respectively. For denial, twin resemblance could be best explained by familial-environmental factors accounting for 19% of the total variation. Genes may affect the vulnerability to psychiatric disorders in part by influencing coping behaviour.

Adaptation, Psychological↗

PubMed1991

The family history method: whose psychiatric history is measured?

OBJECTIVE: The family history method, in which an informant is asked about the history of psychiatric illness in relatives, is widely used in psychiatric research. Previous research has examined the influence on family history information of characteristics of the relative. In this report, the authors seek to clarify the impact on family history reporting of the psychiatric history of the informant. METHOD: Both members of female twin pairs from a population-based twin registry were asked about the history of major depression, generalized anxiety disorder, and alcoholism in their mother and father. The authors examined twin pairs discordant for each of the three diagnoses and predicted that the affected twin would report higher rates of the same disorder in her parent than would the unaffected twin. RESULTS: Twins with a history of major depression or generalized anxiety disorder but not twins with alcoholism were significantly more likely to report the same disorder in their parents than were their unaffected co-twins. CONCLUSIONS: For major depression and generalized anxiety disorder, a family history diagnosis appears to reflect the psychiatric history of both the relative and the informant. Caution may be needed in the interpretation of results based on the family history method, although the magnitude of this problem may be attenuated by the use of multiple informants.

Alcoholism↗

PubMed1990

Estimating familial effects on age at onset and liability to schizophrenia. II. Adjustment for censored data.

Genetic studies of disorders with adult onset often contain individuals who have not completed their age at risk when last observed. Without correction for such censoring, correlation in ages at onset among relatives is substantially underestimated. Moreover, without correction for the effect of correlated ages at onset, the relationship between age at onset in the proband and liability in relatives is substantially overestimated. The present paper describes methods for correcting the effects of censoring on these estimates. In a companion paper [Kendler and MacLean, Genet Epidemiol 7:409-417, 1990] these methods are applied to a large family study of schizophrenia.

Adolescent↗

PubMed1990

Personality and reproductive fitness.

The relationship between reproductive success (number of biological children) and personality was explored in 1101 postmenopausal females from the Australian twin registry. The quadratic response surface relating fitness to extraversion (E) and neuroticism (N) showed a saddle point at intermediate levels of E and N. Selection was shown to be stabilizing, i.e., having an intermediate optimum, along the axis low E, low N-high E, high N and more mildly disruptive, having greater fitness in the extremes, along the axis low N, high E-high N, low E. Neither dimension of personality considered by itself showed a significant linear or quadratic relationship to reproductive success. Sections through the fitness surface, however, show selection tends to favor high neuroticism levels in introverts and low neuroticism levels in extroverts.

Family Characteristics↗

PubMed1990

The analysis of assortative mating: a LISREL model.

The use of linear models to discriminate between primary and secondary assortative mating has allowed a significant advance in our understanding of the mate selection process. We describe how these methods may be implemented in the LISREL and COSAN packages and illustrate the method with data on cognitive ability, education, and personality reported by Phillips et al. (Behav. Genet. 18:347-356, 1988). Issues discussed include the interface between path diagrams and computer program specification, the near-independence of parameters for within-person correlations from parameters for marital correlations, and the fact that almost all of marital resemblance for IQ seems to be due to assortative mating for educational level.

Analysis of Variance↗

PubMed1990

Genetic and environmental effects on self-reported depressive symptoms in a general population twin sample.

To determine the etiology of self-reported depressive symptoms and their co-occurrence in the general population, multivariate genetic models were fitted to the responses of 771 female twin pairs (463 MZ, 308 DZ) to a 20-item epidemiological depression inventory (CES-D scale). A model which contained one common genetic factor, one shared environmental factor, and four unique environmental factors provided a useful account of symptom covariation. Under this model, the four non-shared environmental factors explained the largest proportion of variance in response to the CES-D scale, whereas a single common genetic factor explained substantially less of the variation in symptomatology. Consistent with previous findings (Kendler, Heath, Martin, & Eaves, Archives of General Psychiatry 43, 213-221, 1986) shared environmental influences were found to play a relatively minor role in the report of depressive symptoms. These results suggest that while genetic factors do contribute to the covariation among symptoms of depression, it is the largely non-shared environmental factors that account for the co-occurrence of symptoms in the general population.

Adolescent↗

PubMed1989

Testing structural equation models for twin data using LISREL.

Simple genetic models can be fitted to twin data using software packages such as LISREL (Jöreskog and Sörbom, 1986a). After discussion of data preparation and routine checks on possible violation of assumptions of the twin method, we illustrate univariate, bivariate, and multivariate genetic models which can be tested in cross-sectional twin data using LISREL. These include models for cohort or cohabitation effects, genotype x sex interaction, and certain types of genotype x environment interaction and genotype-environment correlation.

Computer Simulation↗

PubMed1989

Fitting genetic models with LISREL: hypothesis testing.

A brief introduction to the mathematical theory involved in model fitting is provided. The properties of maximum-likelihood estimates are described, and their advantages in fitting structural models are given. Identification of models is considered. Standard errors of parameter estimates are compared with the use of likelihood-ratio (L-R) statistics. For structural modeling, L-R tests are invariant to parameter transformation and give robust tests of significance. Some guidelines for fitting models to data collected from twins are given, with discussion of the relative merits of parsimony and data description.

Computer Simulation↗

PubMed1989

The effects of age, sex, and genotype on self-report drunkenness following a challenge dose of alcohol.

Age is a potential source of variation that contributes to differences between, but not within, twin pairs. In most genetic analyses of twin data, linear and other functions of age are usually removed prior to model fitting. This correction is typically applied only within twin groups of the same sex and zygosity, and no heterogeneity test of age regressions is performed. Here we include age as a variable in the model-fitting procedure and allow for tests of heterogeneity of age regressions across sex and zygosity groups. The LISREL formulation of the approach is illustrated with data collected from Australian twins on subjective impressions of drunkenness following alcohol consumption. The results indicate significant negative covariation of impressions of drunkenness with age. The data support a simple model of additive genetic and unique environmental variation. No evidence was found for sex differences in genetic or environmental components of variation.

Adolescent↗

PubMed1989

Partitioned twin analysis: a power study.

Individual differences in the human genome may now be measured with molecular genetic techniques. Therefore, dizygotic (DZ) twins may be classified as sharing two, one, or zero "genes" identical by descent for any measured polymorphism. As a result, we may partition genetic variation into two sources: (i) genotypes at and closely linked to particular marker loci identified with restriction fragment length polymorphisms (RFLPs) and (ii) other genetic variation. The power of the classical twin study to reject false models lacking either a marker effect or a residual genetic effect is explored. Additivity of genetic effects at or near the locus and of the residual genetic variation as well as random environmental variation are assumed. Results indicate that statistical rejection of models could be achieved with sample sizes which are within the range of several current twin registers. A design including monozygotic (MZ) twins is compared with one consisting of only DZ twins. MZ twins add considerable power for the detection of residual genetic variation but provide no information to resolve genetic marker effects.

Computer Simulation↗