Showing papers by "Michael C. Neale published in 1994"
TL;DR: 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, and a useful approach may be to assess the population with a screening instrument.
Abstract: 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.
294 citations
TL;DR: The transmission of the vulnerability to alcoholism from parents to their daughters is due largely or entirely to genetic factors, with the heritability of liability estimated at 51% to 59%.
Abstract: Objective: The authors seek to understand in general the sources of familial resemblance f or alcoholism and in particular how parents transmit the vulnerability to alcoholism to their daughters. Method: The authors interviewed 1,030 pairs offemale same-sex twins of known zygosity from the population-based Virginia Twin Registry and 1,468 oftheir parents. They examined a narrow definition ofalcoholism, requiring tolerance or dependence, and a threshold approach that classified individuals either as unaffected or as suffering from one of three levels of severity of alcohol-related problems. Twin-family structural equation models were f itted to the observed tetrachoric or polychoric correlation matrices by using asymptotic weighted least squares. Results: In the best-fitting model from both diagnostic approaches, 1) the familial resemblance for alcoholism was due to genetic factors, with the heritability of liability estimated at 51 % to 59%; 2) genetic vulnerability to alcoholism was equally transmitted to daughters from their fathers and from their mothers; and 3) alcoholism in parents was not environmentally transmitted to their children. Assortative mating for alcoholism was found only for the broader definitions of illness. Genetic factors that influenced the liability to alcoholism were the same in the parental and twin generation for the narrow definition of alcoholism. When broader definitions were used, these factors, while substantially correlated, were not identical. Conclusions: The transmission of the vulnerability to alcoholism from parents to their daughters is due largely or entirely to genetic factors.
253 citations
TL;DR: The first application of a fairly general model for family resemblance to data from the Virginia 30,000 is described, showing that the contributions of genes, vertical cultural inheritance, and genotype-environment covariance are all important, but their contributions are significantly heterogeneous over sexes.
Abstract: Received 1 May 1992--Final 28 May 1993 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 faMy 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 cuItural 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.
129 citations
TL;DR: Model-fitting analyses indicate that human parental behavior is under significant genetic influence, and suggests 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.
Abstract: 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.
128 citations
TL;DR: The results suggest that the differential treatment of MZ and DZ twins by their parents is unlikely to represent a significant bias in twin studies of these major psychiatric disorders.
Abstract: The validity of the twin method depends on the equal environment assumption (EEA)--that monozygotic (MZ) and dizygotic (DZ) twins are equally correlated in their exposure to environmental factors of aetiological importance for the trait under study. Parents may treat MZ twins more similarly than DZ twins thereby potentially violating the EEA. We tested this hypothesis for four common psychiatric disorders (major depression, generalized anxiety disorder, phobia, and alcoholism) in a population-based sample of female-female twin pairs where analyses indicate sufficient statistical power meaningfully to test the EEA. Mother's and father's beliefs about their twins' zygosity disagreed with assigned zygosity in approximately 20% of cases, often because of what they were told about their twins' zygosity at their birth. By structural equation model-fitting, we found no evidence that mother's or father's perceived zygosity influenced twin resemblance for any of the disorders. Compared to parents of DZ twins, parents of MZ twins were more likely to report that, in rearing their twins, they emphasized their similarities more than their differences. However, by model-fitting, mothers' and fathers' approach to raising twins had no significant influence on twin resemblance for the four examined psychiatric disorders. These results suggest that the differential treatment of MZ and DZ twins by their parents is unlikely to represent a significant bias in twin studies of these major psychiatric disorders.
110 citations
TL;DR: 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, though causal models with error variance perform almost as well.
Abstract: 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 Virginia 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. © 1994 Wiley-Liss, Inc.
87 citations
TL;DR: Depressive symptoms in adulthood partly reflect enduring characteristics of temperament that are substantially influenced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin.
Abstract: Objective: Self-reported symptoms of depression are commonly used in mental health re search to assess current psychiatric state, yet wide variation in these symptoms among indi viduals has been found in both clinical and epidemiologic populations. The authors sought to understand, from a genetic-epidemiologic perspective, the sources of individual differences in depressive symptoms. Method: Self-reported symptoms of depression were assessed in two samples of twins and their spouses, parents, siblings, and offspring: one sample contained volunteer twins recruited through the American Association of Retired Persons and their rela tives (N=19,203 individuals) and the other contained twins from a population-based twin registry in Virginia and their relatives (N=11,242 individuals). Model fitting by an iterative, diagonal, weighted least squares method was applied to the 80 different family relationships in the extended twin-family design. Results: Independent analyses of the two samples revealed that the level of depressive symptoms was modestly familial, and familial resemblance could be explained solely by genetic factors and spousal resemblance. The estimated heritability of depressive symptoms was between 30% and 37%. There was no evidence that the liability to depressive symptoms was environmentally transmitted from parents to offspring or was in fluenced by environmental factors shared either generally among siblings or specifically be tween twins. With correction for unreliability of measurement, genetic factors accounted for half of the stable variance in depressive symptoms. Conclusions: Depressive symptoms in adulthood partly reflect enduring characteristics of temperament that are substantially influ enced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin. (Am] Psychiatry 1994; 151:1605-1614)
87 citations
TL;DR: Results indicate that use of alcohol is highly familial, with both genetic and shared environmental factors contributing to initiation of alcohol use among men and women, and among drinkers, the degree of twin resemblance for consumption behaviors is low to moderate and appears to be regulated by shared genes rather than shared environments.
Abstract: A growing literature supports genetic contributions to familial resemblance for alcohol use characteristics, but few studies have focused on the mechanisms underlying alcohol use among older persons. We report patterns of alcohol use in a U.S. volunteer sample of 3,049 female and 1,070 male twins aged 50 to 96. Significant gender and age effects were found for self-report measures of current and lifetime alcohol use, with greater intake among males and current and lifetime abstinence more common among older participants. Comparisons with data obtained 4 years previously revealed high stability for quantity and frequency of alcohol consumption. Twin pairs with more frequent social contact tended to be more similar for lifetime and current alcohol use. Biometrical genetic modeling results indicate that use of alcohol is highly familial, with both genetic and shared environmental factors contributing to initiation of alcohol use among men and women. Among drinkers, however, the degree of twin resemblance for consumption behaviors is low to moderate and appears to be regulated by shared genes rather than shared environments. These data are consistent with a multidimensional process, suggesting that the determinants of whether one drinks in older age differ from those underlying how much or how often alcohol is consumed.
70 citations
TL;DR: The implementation of multivariate models of familial resemblance with the Mx package allows for the effects of assortative mating, additive and dominant genes, common and specific environment, and both genetic and cultural transmission between generations.
Abstract: 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.
60 citations
TL;DR: The results suggest that the clinical features of MD can be meaningfully related to the familial vulnerability to illness, particularly with respect to recurrence, impairment and patterns of co-morbidity.
Abstract: Background From both a clinical and an aetiological perspective, major depression (MD) is probably a heterogeneous condition. We attempt to relate these two domains. Method We examined which of an extensive series of clinical characteristics in 646 female twins from a population-based register with a lifetime diagnosis of MD predicts the risk for MD in co-twins. MD was defined by DSM–III–R criteria. Results Four variables uniquely predicted an increased risk for MD in the co-twin: number of episodes, degree of impairment and co-morbidity with panic disorder or bulimia. One variable uniquely predicted decreased risk: co-morbidity with phobia. Variables that did not uniquely predict risk of MD in the co-twin included age at onset, number and kind of depressive symptoms, treatment seeking, duration of the longest episode and co-morbidity with generalised anxiety disorder and alcohol dependence. Conclusions Our results suggest that the clinical features of MD can be meaningfully related to the familial vulnerability to illness, particularly with respect to recurrence, impairment and patterns of co-morbidity.
60 citations
TL;DR: Patterns of alcohol abuse in a community-based U.S. volunteer sample of twins indicate substantial family resemblance for a variety of definitions of lifetime alcohol abuse and alcohol problems.
Abstract: Few studies have employed genetically informative designs to study the causes of alcohol-related problems in nonclinical populations. We report patterns of alcohol abuse in a community-based U.S. volunteer sample of 3,049 female and 1,070 male twins aged 50 to 96. Significant gender and age effects were found for self-report measures of current and lifetime alcohol-related problems, with higher prevalence among males and lower frequency among older birth cohorts. Significant associations were found between severity of alcohol abuse (adapted from Feighner criteria) and age of drinking onset, parental history of alcohol problems and, among males, lower educational attainment. Model-fitting analyses based on data from 650 identical and 479 fraternal twin pairs indicate substantial family resemblance for a variety of definitions of lifetime alcohol abuse and alcohol problems. The median estimate of genetic variance across several definitions of alcohol problems was 38.5%, while that for shared environmental influence was 15.5%. Gender heterogeneity was not found for magnitude of genetic and environmental influences, but these comparisons were limited by low statistical power. Findings are discussed with reference to the literature on alcohol abuse among older adults and the genetic epidemiology of alcoholism.
Journal Article•
TL;DR: Both the genotype and the environment exerted a greater influence on the BMI of black than white adolescents, and the heritability of body mass index was the same for blacks and whites.
Abstract: Although the genetics of relative weight have been investigated in several studies, most of these have been done primarily, if not exclusively, with whites. This study examined the heritability of body mass index (BMI) in 238 pairs of adolescent black and white male and female twins. BMIs were residualized for age and transformed to approximate normality. Hierarchically nested structural equation models were tested. An AE model (A = additive gene effects, E = unique environmental influences) in which the degree to which genetic and environmental factors influence BMI varies by race provided the best fit. Both the genotype and the environment exerted a greater influence on the BMI of black than white adolescents. Thus, although the variances in BMI are greater for blacks, the heritabilities were the same for blacks and whites. Implications for future research are discussed.
TL;DR: The DeFries-Fulker regression model was applied to data on lifetime depression from the Virginia Twin Registry and produced results similar to those from structural equation modeling.
Abstract: 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 ask (affected) and 0 (unaffected). Additive genetic effects are modeled by the predictor variablePR, which equalsP for monozygotic (MZ) andP/2 for dizygotic (DZ) twins; and dominant genetic effects, byPD, which equalsP for MZ andP/4 for DZ twins. By setting an appropriate scale forP (i.e., the value ofk), the regression coefficients ofP, PR, andPD are estimates of the proportions 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.
TL;DR: The stress-buffering effect of perceived support is explored in a large panel survey of adult female twins and no evidence was found for any of the hypotheses investigated to explain the interaction between perceived support and acute stress.
Abstract: The stress-buffering effect of perceived support is explored in a large panel survey of adult female twins. The analysis begins by documenting a significant interaction between perceived support and acute stress in predicting DSM-III-R major depression. Various hypotheses are investigated to explain this interaction. These include the possibilities that the interaction is due to a stress-buffering effect of perceived support which is mediated by received support, that perceived support promotes either the increased use or the increased effectiveness of certain coping strategies, or that there is some underlying genetic factor that affects both the perception of support and adjustment to stress. No evidence was found for any of these hypotheses. The paper closes with a discussion of directions for future research aimed at explaining the interaction between perceived support and acute stress.
TL;DR: Results suggest that random traumatic events and some social learning may be responsible for the onset of BNHI phobias.
Abstract: 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. © 1994 Wiley-Liss, Inc.
TL;DR: This paper shows how models can be simply fitted to such data using programs that can perform genetic analysis of categorical data by maximum likelihood using data on maternal report of the onset of puberty in twin sons from the Virginia Twin Study of Adolescent Behavioral Development.
Abstract: Genetic analysis of variation in age of onset of development milestones or psychopathological behaviors has been little researched, owing largely to the computational difficulty of dealing with “censored” observations. Censored observations arise when the only information on individuals is that they have reached a particular age but without onset having occurred. This paper shows how models can be simply fitted to such data using programs that can perform genetic analysis of categorical data by maximum likelihood. The method is illustrated using the program Mx with data on maternal report of the onset of puberty in twin sons from the Virginia Twin Study of Adolescent Behavioral Development. Frequently, data on age of onset is collected by retrospective recall. This can pose a variety of measurement problems. Suggestions are made for models that account for some of these problems or are robust to their presence. Substantial evidence for “telescoping” of onset dates is found for the puberty data. If left unaccounted for, these effects can artifactually inflate estimates of common environment effects.
TL;DR: This study replicated previous findings showing a high heritability of obesity, as measured by body mass index (kg/m2), using a measure of relative weight that does not assume a constant regression of height on weight across different populations, and evaluated whether there are sex-limited genetic effects.
Abstract: This study replicated previous findings showing a high heritability of obesity, as measured by body mass index (kg/m2), using a measure of relative weight that does not assume a constant regression of height on weight across different populations, and evaluated whether there are sex-limited genetic effects. Subjects were 4,020 adult twin pairs. Alternative causal structural equation models were fitted to variance-covariance matrices. The ADE model (additive genetic effects, dominant/nonadditive genetic effects, and unique environment) fit best. Allowing for sex-specific effects (common sex-limitation model) significantly improved the fit, X2(6) = 230.5, p < .001. The heritability of that portion of weight unrelated to height was large: .61 for men and .73 for women.
TL;DR: The authors consider the potential of combining genetically informative research designs with multivariate longitudinal and experimental methods and consider the appropriateness of the direction of causation (DOG) model, extensions to study causation between the latent variables, sampling of subjects, and heterogeneity.
Abstract: We reply to the commentaries on the lead papers by Neale et al. [1994a] and Duffy and Martin [1994]. Topics covered include power calculations, cross-sectional measurement vs. lifetime reports, the appropriateness of the direction of causation (DOG) model, extensions to study causation between the latent variables, sampling of subjects, and heterogeneity. We consider the potential of combining genetically informative research designs with multivariate longitudinal and experimental methods. (C) 1994 Wiley-Liss, Inc.
TL;DR: This model is extended to cover data collected from relatives, where the observations are not independent and further extensions of the model are developed that permit tests of several assumptions implicit in multiple regression.
Abstract: Multiple regression is a causal model of the relationship between sets of independent (X) and dependent (Y) variables. This model is extended to cover data collected from relatives, where the observations are not independent. If correct, the model permits appropriate statistical tests of regression coefficients in data collected from relatives. Across relative covariances, particularly across the independent and dependent variables may reject the basic regression model. Further extensions of the model are developed that permit tests of several assumptions implicit in multiple regression: (a) the assignment of variables as dependent or independent; (b) the relationship between X and Y variables is not due to some latent variable which causes variation in both; and (c) there is no reciprocal interaction between the X and the Y variables. Discrimination between these alternatives is especially strong if data are collected from more than one class of relative, which differ in their X and Y variable covariance structure. Data on Eysenck Extraversion, Neuroticism and CESD depression collected from twins are used as an illustrative example.
TL;DR: If the syndrome of GAD is to be narrowed, it would, from a familial perspective, be more valid to increase the minimum number of required symptoms rather than to increased the minimum duration of illness.
Abstract: The authors seek to determine whether the clinical characteristics of generalized anxiety disorder (GAD) differ in individuals with a high vs low familial vulnerability to illness We identified 486 personally interviewed female twins from a population-based register who had both an interviewed co-twin and a lifetime history of GAD using modified DSM-III-R criteria which required a one-month minimum duration of illness We attempted to predict risk for GAD in the co-twin from the clinical features of the GAD in the proband twin using the Cox proportional hazard model, controlling for year of birth and zygosity Only two variables uniquely predicted an increased risk for GAD in the co-twin: number of GAD symptoms endorsed and comorbidity with bulimia Variables that did not uniquely predict risk of illness in the co-twin included age at onset, duration of the longest episode and number of episodes The familial vulnerability to GAD can be meaningfully indexed by clinical features of the syndrome These results suggest that if the syndrome of GAD is to be narrowed, it would, from a familial perspective, be more valid to increase the minimum number of required symptoms rather than to increase the minimum duration of illness