Showing papers by "Michael C. Neale published in 2000"
TL;DR: A meta-analysis of relevant data from primary studies of the genetic epidemiology of major depression suggested that familial aggregation was due to additive genetic effects, with a minimal contribution of environmental effects common to siblings and substantial individual-specific environmental effects/measurement error.
Abstract: OBJECTIVE: The authors conducted a meta-analysis of relevant data from primary studies of the genetic epidemiology of major depression.METHOD: The authors searched MEDLINE and the reference lists of previous review articles to identify relevant primary studies. On the basis of a review of family, adoption, and twin studies that met specific inclusion criteria, the authors derived quantitative summary statistics. RESULTS: Five family studies met the inclusion criteria. The odds ratios for proband (subjects with major depression or comparison subjects) versus first-degree relative status (affected or unaffected with major depression) were homogeneous across the five studies (Mantel-Haenszel odds ratio=2.84, 95% CI=2.31–3.49). No adoption study met the inclusion criteria, but the results of two of the three reports were consistent with genetic influences on liability to major depression. Five twin studies met the inclusion criteria, and their statistical summation suggested that familial aggregation was due ...
2,958 citations
TL;DR: Twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
Abstract: Background In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. Methods In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. Results Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the equal environment assumption. Conclusions In accord with prior results in studies of women, the family environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
462 citations
TL;DR: The results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexic and major depression.
Abstract: OBJECTIVE: The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. METHOD: They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. RESULTS: Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%–84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. CONCLUSIONS: Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.
363 citations
TL;DR: A large population-based twin sample from the Australian Twin Registry was screened to identify twin pairs in which one or both members reported themselves to be affected by stuttering, and approximately 70% (95% confidence interval: 39–86%) of the variance in liability to stuttering was found to be attributable to additive genetic effects, with the remainder due to nonshared environmental effects.
Abstract: Stuttering is a developmental disorder of speech production that usually emerges in childhood. In this study, a large population-based twin sample from the Australian Twin Registry (1567 pairs and 634 singles aged 17‐29 years) was screened to identify twin pairs in which one or both members reported themselves to be affected by stuttering. Telephone interview-based diagnoses were obtained for 457 of these individuals (self-reported affected cases, cotwins, and controls) to determine whether the self-report was correct. To correct for ascertainment bias we carried out a bivariate analysis of the final diagnosis in the selected sample with the screening item in the full sample, using the categorical raw data option of Mx 1.47c. After correcting for ascertainment bias, approximately 70% (95% confidence interval: 39‐86%) of the variance in liability to stuttering was found to be attributable to additive genetic effects, with the remainder due to nonshared environmental effects.
163 citations
TL;DR: In this article, genetic, shared and unique environmental, and rater bias effects were estimated for the AP, Aggressive, and AxD syndromes for 492 twin pairs assessed with the Child Behavior Checklist.
Abstract: Objective To estimate genetic, environmental, and rater contrast influences on parental report of Attention Problems (AP), Aggressive (Agg), and Anxious/Depressed (AxD) behaviors of 492 twin pairs assessed with the Child Behavior Checklist. Method A parent (92% mothers) of twins aged 8 to 12 years completed the Child Behavior Checklist. Genetic, shared and unique environmental, and rater bias effects were estimated for the AP, Agg, and AxD syndromes. Data on boys and girls were analyzed separately. Results were compared to prior research on related DSM disorders. Results Estimates of genetic influences on AP (60%-68%), Agg (70%-77%), and AxD (61%-65%) were high for both sexes, but lower for AP than prior findings using DSM attention-deficit hyperactivity disorder (ADHD). However, unlike equivalent analyses of DSM ADHD based on parental report, there was no evidence of rater bias. Conclusions Estimates of genetic influence on these common child psychopathological domains were high. There was no evidence of rater contrast effects. These findings have implications for diagnosis, particularly when assessing families with multiple children.
139 citations
TL;DR: A multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height suggests that cerebellary volume and intrac Cranial space vary with age and sex.
Abstract: The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.
137 citations
TL;DR: Methods to fit structured latent growth curves to data from MZ and DZ twins and focus on the estimation of genetic and environmental variation and covariation in each of the asymptote, initial and rate of growth factors are described.
Abstract: We describe methods to fit structured latent growth curves to data from MZ and DZ twins. The well-known Gompertz, logistic and exponential curves may be written as a function of three components-asymptote, initial value, and rate of change. These components are allowed to vary and covary within individuals in a structured latent growth model . Such models are highly economical, requiring a small number of parameters to describe covariation across many occasions of measurement. We extend these methods to analyse longitudinal data from MZ and DZ twins and focus on the estimation of genetic and environmental variation and covariation in each of the asymptote, initial and rate of growth factors. For illustration, the models are fitted to longitudinal Bayley Infant Mental Development Scale data published by McArdle (1986). In these data, al l three components of growth appear strongly familial with the majority of variance associated with the shared environment; differences between the models were not great. Occasionspecific residual factors not associated with the curve components account for approximately 40% of variance of which a significant proportion is additive genetic. Though the growth curve model fit less well than some others, they make restrictive, falsifiable predictions about the mean, variance and twin covariance of other (not yet measured) occasions of measurement.
90 citations
TL;DR: Five novel single nucleotide polymorphisms (SNPs) were found and none of the four polymorphisms the authors tested, nor their estimated haplotypes, were associated with smoking initiation or progression to nicotine dependence.
Abstract: Several types of evidence, including experiments with mice that lack the nicotinic acetylcholine receptor beta2-subunit gene (CHRNB2), have suggested that a beta2-containing nicotinic receptor is necessary for at least some of the reinforcing properties of nicotine. However, sequence variations in CHRNB2 have not been reported, and its role in influencing human smoking behavior and nicotine dependence is not known. We screened most of the introns and exons and found five novel single nucleotide polymorphisms (SNPs). We tested four of these SNPs in three large, carefully selected samples: nonsmokers (n = 317) and regular smokers low levels of nicotine dependence (ND, n = 238), or smokers with high-ND (n = 317). None of the four polymorphisms we tested, nor their estimated haplotypes, were associated with smoking initiation or progression to nicotine dependence.
84 citations
TL;DR: Examination of the covariance between twins classified according to allele sharing indicates that the association is not due to population stratification, but to a genuine effect of the ApoE locus on levels, which accounts for only one‐fourth of the genetic variation inApoE levels.
Abstract: ApoE levels and chromosome 19 ApoE polymorphisms were measured in a sample of 156 Dutch families. Each pedigree consisted of parents aged 35-65 years and their twin offspring aged 14-21 years. A significant effect of the chromosome 19 apoE locus on quantitative plasma levels of apolipoprotein E was observed. The ApoE polymorphism explained 16% of the variance in ApoE levels. Tests of association of ApoE levels with the apoC1 locus, which is in complete linkage disequilibrium with the ApoE locus, also showed a significant effect, although the variance explained by ApoC1 was only 1%. Examination of the covariance between twins classified according to allele sharing indicates that the association is not due to population stratification, but to a genuine effect of the ApoE locus on levels. However, the ApoE locus accounts for only one-fourth of the genetic variation in ApoE levels.
30 citations
TL;DR: Secular changes in sociodemographic factors responsible for increasing rates of CD may also account for the greater magnitude of shared environmental influences on variation in CD found among more recent cohorts.
Abstract: Background. Rates of child and adolescent conduct disorder (CD) have increased steadily over the past several decades. What is not known is whether the underlying genetic and environmental influences on individual differences in CD have also changed. Methods. Retrospective reports of antisocial behaviour prior to age 18 were obtained from a population-based sample of 2769 adult males from male–male twin pairs born between 1940 and 1974. Using a summary score of number of CD symptoms, structural equation modelling was used to investigate whether mean level and variation in CD increased with more recent cohorts, and whether any increase in variance could be explained by familial or non-familial factors. Results. Both mean level CD symptoms and variation were increased in more recent cohorts. Model fitting indicated that the primary increase in variance was due to familial factors, most notably, an increase in the shared environmental influences on CD, from 0·01 (95% CI = 0·00; 0·27) to 0·30 (95% CI = 0·01; 0·44). Heritability estimates remained largely unchanged, although an increase in genetic factors could not be ruled out. Conclusions. Secular changes in sociodemographic factors responsible for increasing rates of CD may also account for the greater magnitude of shared environmental influences on variation in CD found among more recent cohorts.
29 citations
TL;DR: Findings suggested considerable overlap between the genetic risk factors for the development of binge eating and the genetic Risk Factors for the transition from binge eating to bulimia nervosa, and nonshared environment may be important in influencing the risk for bulimic nervosa once binge eating is initiated.
Abstract: This study investigated the differential risk factors for the initiation of binge eating and the transition from binge eating to bulimia nervosa. Women from a population-based twin registry (850 complete pairs) were assessed with respect to specific measured variables (including demographics, religiosity, lifetime psychopathology, current symptomatology, and personality) and latent genetic and environmental variables. Because of the relative rarity of bulimia nervosa, statistical power was low, but findings suggested considerable overlap between the genetic risk factors for the development of binge eating and the genetic risk factors for the transition from binge eating to bulimia nervosa. Genetic risk factors for binge eating and bulimia nervosa may be largely similar, whereas nonshared environment may be important in influencing the risk for bulimia nervosa once binge eating is initiated.
TL;DR: While genetic factors appear to be of moderate etiologic importance in all major dimensions of mental health, the family environment is an important influence on only interpersonal relations, social support, and substance use.
Abstract: OBJECTIVE: While researchers have increasing insight into the role of genetic and environmental factors in the etiology of psychiatric and substance use disorders, they know much less about how such factors influence the dimensions of healthy psychological functioning. METHOD: In a population-based sample of 794 female-female twin pairs, the authors examined, by using multivariate structural equation modeling, six dimensions of mental health: perceived physical health, nonconflictual interpersonal relationships, anxious-depressive symptoms, substance use, social support, and self-esteem. RESULTS: The best-fit model was complex and constituted five common factors (two genetic, one family environmental, and two unique environmental); variable-specific genetic effects for physical health, substance use, and social support; and variable-specific family environmental effects for interpersonal relationships and substance use. Genetic effects were seen for all six dimensions; total heritabilities ranged from 16%...
TL;DR: Whether intra‐pair differences in birth weight predicts discordance for adult psychiatric disorders in 527 female monozygotic twin pairs from a population‐based twin registry is examined.
Abstract: The study of discordant monozygotic twins may identify important developmental risk factors for adult psychiatric disorder. Differential experience in utero is one candidate environmental risk factor that may distinguish monozygotic twins. In this report, we examine whether intra-pair differences in birth weight predicts discordance for adult psychiatric disorders in 527 female monozygotic twin pairs from a population-based twin registry. Twins were personally interviewed about their lifetime history of DSM-III-R alcoholism, anorexia nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic disorder, social phobia and simple phobia. Birth weight was estimated from birth certificates, or from retrospective maternal, paternal and self-reports. Conditional logistic regression is used to characterize the association between intra-pair differences in birth weight and discordance for psychiatric disorder in monozygotic twins. The twin with the heavier birth weight in discordant pairs is (insignificantly) more likely to have a history of alcoholism or bulimia. The twin with the lighter birth weight in discordant pairs is (insignificantly) more likely to have a history of major depression, simple phobia, panic disorder, anorexia nervosa, social phobia or generalized anxiety disorder. For all psychiatric disorders examined, the lighter (or heavier) co-twin at birth is not systematically the affected twin within discordant pairs.
TL;DR: This article describes the implementation of joint linkage and association using Mx, in both path diagram and script formats, and discusses a number of possible extensions to the model.
Abstract: Evidence for genetic linkage, obtained from a correlation between phenotypic similarity and genetic similarity at a specific chromosomal location typically yields a broad genomic region in which a candidate locus might be found. Evidence for association is usually gathered from case control studies and is subject to false positives from phenomena such as population stratification. Data from relatives may be used to distinguish population stratification from genuine allelic effects in an association context. Of special interest is joint linkage and association which may be used for fine mapping because evidence for linkage will be reduced in the presence of evidence for association. This article describes the implementation of these methods using Mx, in both path diagram and script formats, and discusses a number of possible extensions to the model.