Biomedical subjects

M C Neale

Publications and source records attributed to M C Neale.

At least 91 records · Page 5Linked to original sources

PubMed1995

Genetic, environmental, and phenotypic links between body mass index and blood pressure among women.

Greater relative weight is associated with higher blood pressure, but the reasons are unknown. The inability of current technology to induce sustained weight loss among overweight persons precludes experimental tests of whether this association is causal. We evaluated the degree to which the covariation between body mass index (BMI; kg/m2) and blood pressure (BP) among women is due to pleiotropic genetic factors, environmental factors, or phenotypic causation. The sample included 75 monozygotic (MZ) and 39 dizygotic (DZ) pairs of adult female twins. "BP" was calculated as the unit-weighted mean of systolic and diastolic. Data were analyzed through structural equation modeling. A model was specified stipulating that additive genetic effects (A) and unique environmental effects (E) each contributed to the covariance between BMI and BP, thus allowing for both pleiotropic and unique environmental influences on the covariance between BMI and BP. Dropping the pleiotropic influences significantly worsened the model (chi 2 = 4.62, df = 1, P = .032), suggesting significant pleiotropic effects. Dropping the environmental influences on the cross-phenotype covariance did not significantly worsen the model (chi 2 = 1.42, df = 1, P = .233). This indicates no significant effect of the environment on the covariance between BMI and BP. Finally, a model of phenotypic causation in which BMI directly influenced BP was fitted. This model provided the best single parameter explanation of the BP-BMI covariation. These data suggest that, among women, regardless of the source of variation, changes in BMI should lead to long-standing changes in BP.

Adult↗

PubMed1995

The structure of the genetic and environmental risk factors for six major psychiatric disorders in women. Phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism.

BACKGROUND: Although prior family and twin studies have examined the relationship between the genetic and environmental risk factors for pairs of psychiatric disorders, the interrelationship between these classes of risk factors for a broad range of psychiatric disorders remains largely unknown. METHODS: An epidemiologic sample of 1030 female-female twin pairs with known zygosity, ascertained from the Virginia Twin Registry, were evaluated by a personal interview conducted by mental health professionals, assessing lifetime history of phobia, generalized anxiety disorder, panic disorder, bulimia nervosa, major depression, and alcoholism. RESULTS: A multivariate twin analysis suggested the following. First, genetic, familial-environmental, and individual-specific environmental risk factors each cause a unique pattern of comorbidity among the six disorders. Second, genetic influences on these disorders are best explained by two factors, the first of which loads heavily on phobia, panic disorder, and bulimia nervosa and the second, on major depression and generalized anxiety disorder. Third, unlike other disorders, genetic influences on alcoholism are largely disorder specific. Fourth, familial-environmental influences on these disorders are best explained by a single factor that substantially influenced liability to bulimia nervosa only. Fifth, individual-specific environmental influences on the risk for these psychiatric disorders are best explained by a single factor, with highest loadings on generalized anxiety disorder and major depression and with large-disorder-specific loadings, especially on phobias, panic disorder, and alcoholism. CONCLUSIONS: These results support the following hypotheses: First, each major risk factor domain (genes, family environment, and individual-specific environment) influences comorbidity between these disorders in a distinct manner. Second, genetic influences on these six disorders are neither highly specific nor highly nonspecific. Neither a model that contains a discrete set of genetic factors for each disorder nor a model in which all six disorders results from a single set of genes is well supported. Third, the anxiety disorders are not, from a genetic perspective, etiologically homogeneous. Fourth, most of the genetic factors that influence vulnerability to alcoholism in women do not alter the risk for development of other common psychiatric disorders. These results should be interpreted in the context of both the strengths and limitations of multivariate twin analysis.

Adult↗

PubMed1995

A pilot Swedish twin study of affective illness including hospital- and population-ascertained subsamples: results of model fitting.

We investigated the heritability of liability to affective illness (AI) in twins ascertained through psychiatric hospitalization for AI from the Swedish Psychiatric Twin Registry and from the general population Swedish Twin Registry. Lifetime diagnoses were assessed by mailed questionnaire containing, in self-report format, DSM-III-R criteria for mania and major depression (MD). Jointly analyzing both subsamples using Mx, and assuming a multifactorial threshold model, the best-fitting twin model using narrow diagnostic criteria suggested that the liability to AI could be explained by additive genetic effects, with an estimated heritability of liability of 64%, and individual-specific environment. Using broad criteria, results were similar except that the estimated broad heritability of liability was higher (83%) and due largely to dominance genetic effects. Fitting sex-dependent models suggested that the same genetic and environmental factors influenced liability to AI in men and women to the same degree, although women had a lower threshold of manifestation. These results suggested that in Sweden, AI is a highly heritable syndrome and family resemblance is due largely or entirely to genetic factors.

Adult↗

PubMed1995

Physical similarity and the equal-environment assumption in twin studies of psychiatric disorders.

The equal-environment assumption (EEA), upon which twin methodology is based, was examined for the impact of physical similarity on phenotypic resemblance in five common psychiatric disorders: major depression, generalized anxiety disorder, phobia, alcoholism, and bulimia. A population-based sample of 882 female-female twin pairs of known zygosity was rated for similarity of appearance by color photographs. Psychiatric diagnoses were made by clinical assessment of personal interviews of the twins. Structural equation modeling of the data using physical similarity as a form of specified common environment provided no evidence for a significant effect of physical resemblance on concordance for major depression, generalized anxiety disorder, phobia, and alcoholism, thereby supporting the validity of the EEA in twin studies of these disorders. Results for bulimia, on the other hand, suggest, within the limitations of this study, that physical similarity may significantly influence twin resemblance for this disorder.

Adolescent↗

PubMed1995

A twin-family study of self-report symptoms of panic-phobia and somatization.

Self-report symptoms of anxiety are widely used in mental health and social science research as an index of current psychiatric state. Previous twin studies have suggested that genetic factors account for a significant proportion of the variance in these symptoms. To replicate and extend these findings, we examined self-report symptoms of panic-phobia and somatization in the "Virginia 30,000" twin-family sample. Model fitting applied to 80 unique relationships in the twin-family pedigree produced the following major results: (i) genetic effects were significant for both symptom factors, accounting for between 25 and 49% of the total variance, with the exception of symptoms of panic-phobia in females, where they accounted for 15-16% of the variance; (ii) familial environmental effects were absent for symptoms of somatization, while for symptoms of panic-phobia they accounted for a very small proportion of variance in males (< or = 1.2%) and a modest proportion in females (6-17%); (iii) spousal correlations were present for both factors, ranging from +0.05 to +0.20; (iv) genetic factors which influenced symptoms were generally the same in males and females, although their effect was greater in males; (v) heritability estimates were lower in the population-based than in the volunteer sample; and (vi) when test-retest reliability was included in the model, results suggest that genetic factors account for at least half of the stable variance for all symptom factors, except panic-phobia in females. Our results support the validity of previous twin studies of self-report symptoms of anxiety and suggest that genetic factors significantly influence these symptoms but familial-environmental factors play little or no etiologic role.

Adult↗

PubMed1995

A twin study of generalized anxiety disorder and major depression.

Previous analyses with a sample of female twins sampled from the general population in Virginia have suggested that generalized anxiety disorder (GAD) and major depression (MD) share their genetic determinants but have partly different environmental determinants. The goal of this report is to examine whether these findings apply to samples that include male as well as female twins and contain high proportions of subjects who had been hospitalized for MD. The subjects were ascertained through two different sources: (i) index probands were ascertained through the Swedish Psychiatric Twin Registry for a diagnosis of unipolar or bipolar affective illness; (ii) control twin probands were ascertained through the Swedish Twin Registry. Subjects were sent questionnaires for the assessment of lifetime history of GAD and MD. Positing multinormal distribution of the liability for GAD and MD, we fitted bivariate models to examine the sources of comorbidity. The full model included additive genetic effects, shared environment and individual-specific environment, as well as scalar and non-scalar sex limitations and different thresholds across genders. The best-fitting model included: (i) a genetic correlation of unity; (ii) no common environment; (iii) an individual-specific environmental correlation of 0.28; (iv) different thresholds across genders, but neither scalar nor non-scalar sex-limitations. A model that included additive and dominant genetic effects and individual-specific environment, with correlation of unity for both additive and dominant genetic effects, provided an equivalent fit. These analyses confirm that GAD and MD share the same genetic factors but that their environmental determinants are mostly distinct. Moreover, the present report supports the feasibility of combining clinical ascertained and general-population samples into a single bivariate analysis.

Adult↗

PubMed1995

Evaluating the spectrum concept of schizophrenia in the Roscommon Family Study.

OBJECTIVE: The authors sought to evaluate whether the pattern of schizophrenia and related disorders in probands and their relatives can be explained by a single underlying continuum of liability to the "schizophrenia spectrum." METHOD: In the epidemiologically based Roscommon Family Study, the authors separately examined--in siblings, parents, and relatives of index and comparison probands--the familial aggregation and coaggregation of five hierarchically defined disorders: schizophrenia, schizoaffective disorder, schizotypal/paranoid personality disorder, other nonaffective psychoses, and psychotic affective illness. A multiple threshold model was fitted to these contingency tables by maximum likelihood. RESULTS: The multiple threshold model that constrained resemblance to be the same in siblings and parents fit the data well and estimated the correlation in liability to schizophrenia spectrum disorders between probands and first-degree relatives at 0.36. Parents, however, required higher levels of liability to manifest schizophrenia spectrum disorders than siblings. While schizophrenia and psychotic affective illness could be clearly assigned to the two extremes of the schizophrenia spectrum, the proper ordering of schizoaffective disorder, schizotypal/paranoid personality disorder, and other nonaffective psychoses could not be unambiguously determined. CONCLUSIONS: These results are consistent with the existence of a schizophrenia spectrum in which these five disorders are manifestations, of varying severity, of the same underlying vulnerability. This vulnerability is strongly transmitted within families.

Adult↗

PubMed1995

Stressful life events, genetic liability, and onset of an episode of major depression in women.

OBJECTIVE: This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression. METHOD: Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression. RESULTS: Nine "personal" and three aggregate "network" stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of > 10 and were termed "severe": death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indicated significant Genotype by Environment interaction in the prediction of onset of major depression. CONCLUSIONS: Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.

Adult↗

PubMed1995

Genetic covariance structure of incisor crown size in twins.

Previous studies of tooth size in twins and their families have suggested a high degree of genetic control, although there have been difficulties separating the various genetic and environmental effects. A genetic analysis of variation in crown size of the permanent incisors of South Australian twins was carried out, with structural equation modeling used to determine the relative contributions of genetic and environmental factors. Maximum mesiodistal crown dimensions of maxillary and mandibular permanent incisors were recorded from dental models of 298 pairs of twins, including 149 monozygous (MZ) and 149 dizygous (DZ) pairs. The analysis revealed that: (i) an adequate fit required additive genetic and unique environmental components; (ii) augmenting the model with non-additive genetic variation did not lead to a significant improvement in fit; (iii) there was evidence of shared environmental influences in the upper central incisors of males; (iv) the additive genetic component constituted a general factor loading on all eight teeth, with group factors loading on antimeric pairs of teeth; (v) unique environmental effects were mostly variable-specific; (vi) most factor loadings on antimeric tooth pairs could be constrained to be equal, indicating a symmetry of genetic and environmental influences between left and right sides; and (vii) estimated heritability of the incisor mesiodistal dimensions varied from 0.81 to 0.91.

Adolescent↗

PubMed1995

The genetic epidemiology of self-esteem.

BACKGROUND: Previous studies on self-esteem have focused exclusively on its psychosocial determinants. The goal of the present study is to clarify genetic v. environmental determinants of self-esteem. METHOD: Participants were Caucasian women sampled from the Virginia Twin Register: 363 pairs of MZ and 238 pairs of DZ twins were available from the first wave of the study, and 430 pairs of MZ and 308 pairs of DZ twins from the second. Self-esteem was assessed with the Rosenberg's Self-Esteem Scale. RESULTS: Using univariate twin analyses of self-esteem and a repeated measurement twin model, we found that self-esteem is a moderately heritable trait (heritability = 52% in the repeated measurement model); environmental influences are also very important, and are probably mostly not shared by members of a twin pair. CONCLUSIONS: Aetiological models of self-esteem which examine only psychosocial factors are incomplete; genetic factors need to be integrated.

Adult↗

PubMed1995

Models of comorbidity for multifactorial disorders.

We develop several formal models for comorbidity between multifactorial disorders. Based on the work of D. N. Klein and L. P. Riso, the models include (i) alternate forms, where the two disorders have the same underlying continuum of liability; (ii) random multiformity, in which affection status on one disorder abruptly increases risk for the second; (iii) extreme multiformity, where only extreme cases have an abruptly increased risk for the second disorder; (iv) three independent disorders, in which excess comorbid cases are due to a separate, third disorder; (v) correlated liabilities, where the risk factors for the two disorders correlate; and (vi) direct causal models, where the liability for one disorder is a cause of the other disorder. These models are used to make quantitative predictions about the relative proportions of pairs of relatives who are classified according to whether each relative has neither disorder, disorder A but not B, disorder B but not A, or both A and B. For illustration, we analyze data on major depression (MD) and generalized anxiety disorder (GAD) assessed in adult female MZ and DZ twins, which enable estimation of the relative impact of genetic and environmental factors. Several models are rejected--that comorbid cases are due to chance; multiformity of GAD; a third independent disorder; and GAD being a cause of MD. Of the models that fit the data, correlated liabilities, MD causes GAD, and reciprocal causation seem best. MD appears to be a source of liability for GAD. Possible extensions to the models are discussed.

Adult↗

PubMed1994

Genetics of blood-injury fears and phobias: a population-based twin study.

Data on unreasonable fears of blood, needles, hospitals, and illness (BNHI) were collected by telephone interview from 541 MZ and 388 DZ pairs of female twins from the population-based Virginia Twin Registry. BNHI phobia was defined as the presence of fear accompanied by interference. Age at onset of phobia was found to be very similar to that of situational phobias previously assessed in the sample. Using a multiple threshold model, we found no evidence for qualitative differences between BNHI fears and BNHI phobia. The familial aggregation of fears appears to be entirely due to additive genetic variance. The possible exception to this is fear of illness, which, like BNHI phobias, seems to aggregate within families because of shared environmental factors. Although power to discriminate between the causes of familial resemblance is low, results suggest that random traumatic events and some social learning may be responsible for the onset of BNHI phobias. About two-thirds of variance is individual-specific environmental, and could include genotype x environment interaction and measurement error.

Age of Onset↗

PubMed1994

Depression and parental bonding: cause, consequence, or genetic covariance?

It is shown how information on the direction of causation between variables may be obtained from a cross-sectional study of pairs of relatives. This method is applied to the study of the relationship between ratings of parents' rearing style and depression in their offspring. Adult female twins ascertained from a population-based registry in Viroffia completed the Center for Epidemiological Studies--Depression Scale (CESD) and a 7-item short form of the Parental Bonding Instrument (PBI) about each of their parents. Two dimensions of parental behavior, overprotectiveness and coldness, were analyzed jointly with depression data in both genetic factor and directional genetic models. Models that specify ratings of parents as a cause of depression in the offspring fit the data significantly better than models that specify depression as a cause of ratings of parents. A still better fit is obtained with models that specify common genetic variance to depression and ratings, though causal models with error variance perform almost as well. In general, ratings of fathers show more genetic and less shared environmental variance than ratings of mothers, which might arise from more consistent treatment of offspring by mothers than by fathers. No effect of children eliciting parental rearing style was detected with these data. The relative merits of instrumental variable, longitudinal, and family approaches to testing causal models are discussed.

Adult↗

PubMed1994

Logistic regression analysis of twin data: estimation of parameters of the multifactorial liability-threshold model.

We extend the DeFries-Fulker regression model for the analysis of quantitative twin data to cover binary traits and genetic dominance. In the proposed logistic regression model, the cotwin's trait status, C, is the response variable, while the proband's trait status, P, is a predictor variable coded as k (affected) and 0 (unaffected). Additive genetic effects are modeled by the predictor variable PR, which equals P for monozygotic (MZ) and P/2 for dizygotic (DZ) twins; and dominant genetic effects, by PD, which equals P for MZ and P/4 for DZ twins. By setting an appropriate scale for P (i.e., the value of k), the regression coefficients of P, PR, and PD are estimates of the proportion of variance in liability due to common family environment, additive genetic effects, and dominant genetic effects, respectively, for a multifactorial liability-threshold model. This model was applied to data on lifetime depression from the Virginia Twin Registry and produced results similar to those from structural equation modeling.

Adult↗

PubMed1994

The power of the classical twin study to resolve variation in threshold traits.

We explore the power of the twin study to resolve sources of familial resemblance when the data are measured at the binary or ordinal level. Four components of variance were examined: additive genetic, nonadditive genetic, and common and specific environment. Curves are presented to compare the power of the continuous case with those of threshold models corresponding to different prevalences in the population: 1, 5, 10, 25, and 50%. Approximately three times the sample size is needed for equivalent power to the continuous case when the threshold is at the optimal 50%, and this ratio increases to about 10 times when 10% are above threshold. Some power may be recovered by subdividing those above threshold to form three or more ordered classes, but power is determined largely by the lowest threshold. Non-random ascertainment of twins (i) through affected twins and examining their cotwins or (ii) through ascertainment of all pairs in which at least one twin is affected increases power. In most cases, strategy i is more efficient than strategy ii. Though powerful for the rarer disorders, these methods suffer the disadvantage that they rely on prior knowledge of the population prevalence. Furthermore, sampling from hospital cases may introduce biases, reducing their value. A useful approach may be to assess the population with a screening instrument; the power calculations indicate that sampling all concordant and half of the discordant pairs would be efficient, as along as the cost of screening is not too high.

Bias↗

PubMed1994

Human parental behavior: evidence for genetic influence and potential implication for gene-culture transmission.

A large sample of adult twins (1117 pairs), who were concordant for having had children were asked to report on their child-rearing practices. A 14-item version of the Parental Bonding Instrument (PBI) was used to assess rearing practices of parent twins. The two factors of Care and Overprotection, commonly found in other studies, were recovered from this analysis of the PBI's parent form. Model-fitting analyses indicate that human parental behavior is under significant genetic influence. Findings further suggest that this influence is sex limited, with a higher heritability in mothers than in fathers, and that it may result partly from the expression of dominant genes. For both PBI factors and both parents, the best-fitting models invariably assumed sex-limited genetic effects and unique environmental influences only. Broad heritability ranged from 19% (father overprotection) to 39% (mother care). These results are interpreted in the broader perspective of gene-culture theory.

Adult↗

PubMed1994

Multivariate genetic analysis of twin-family data on fears: Mx models.

We describe the implementation of multivariate models of familial resemblance with the Mx package. The structural equation models allow for the effects of assortative mating, additive and dominant genes, common and specific environment, and both genetic and cultural transmission between generations. Two approaches are compared: a correlational one based on Fulker and a factor model described by Phillips and Fulker. Both are illustrated by application to published data on social fears and fear of leadership measured in monozygotic and dizygotic twins and their parents. In the example data, genetic dominance yields a more parsimonious explanation of the data than does cultural transmission, although neither is needed to obtain a good fit to the data. A model of reduced genetic correlation between generations also fits the data but has inherent limitations in this sample. Extensions to sex-limitation and more complex models are discussed.

Adult↗

PubMed1994

A model system for analysis of family resemblance in extended kinships of twins.

The "Virginia 30,000" comprise 29,698 subjects from the extended kinships of 5670 twin pairs. Over 80 unique correlations between relatives can be derived from these kinships, comprised of monozygotic (MZ) and dizygotic (DZ) twins and their spouses, parents, siblings, and children. This paper describes the first application of a fairly general model for family resemblance to data from the Virginia 30,000. The model assesses the contributions of additive and dominant genetic effects in the presence of vertical cultural inheritance, phenotypic assortative mating, shared twin and sibling environments, and within-family environment. The genetic and environmental effects can be dependent on sex. Assortment and cultural inheritance may be based either on the phenotype as measured or on a latent trait of which the measured phenotype is an unreliable index. The model was applied to church attendance data from this study. The results show that the contributions of genes, vertical cultural inheritance, and genotype-environment covariance are all important, but their contributions are significantly heterogeneous over sexes. Phenotypic assortative mating has a major impact on family resemblance in church attendance.

Adult↗