Biomedical subjects

M C Neale

Publications and source records attributed to M C Neale.

At least 127 records · Page 7Linked to original sources

PubMed1993

Analyzing twin resemblance in multisymptom data: genetic applications of a latent class model for symptoms of conduct disorder in juvenile boys.

A model based on the latent class model is developed for the effects of genes and environment on multivariate categorical data in twins. The model captures many essential features of dimensional and categorical conceptions of complex behavioral phenotypes and can include, as special cases, a variety of major locus models including those that allow for etiological heterogeneity, differential sensitivity of latent classes to measured covariates, and genotype x environment interaction (G x E). Many features of the model are illustrated by an application to ratings on eight items relating to conduct disorder selected from the Rutter Parent Questionnaire (RPQ). Mothers rated their 8- to 16-year-old male twin offspring [174 monozygotic (MZ) and 164 dizygotic (DZ) pairs]. The impact of age on the frequency of reported symptoms was relatively slight. Preliminary latent class analysis suggests that four classes are required to explain the reported behavioral profiles of the individual twins. A more detailed analysis of the pairwise response profiles reveals a significant association between twins for membership of latent classes and that the association is greater in MZ than DZ twins, suggesting that genetic factors played a significant role in class membership. Further analysis shows that the frequencies of MZ pairs discordant for membership of some latent classes are close to zero, while others are definitely not zero. One possible explanation of this finding is that the items reflect underlying etiological heterogeneity, with some response profiles reflecting genetic categories and others revealing a latent environmental risk factor. We explore two "four-class" models for etiological heterogeneity which make different assumptions about the way in which genes and environment interact to produce complex disease phenotypes. The first model allows for genetic heterogeneity that is expressed only in individuals exposed to a high-risk ("predisposing") environment. The second model allows the environment to differentiate two forms of the disorder in individuals of high genetic risk. The first model fits better than the second, but neither fits as well as the general model for four latent classes associated in twins. The results suggest that a single-locus/two-allele model cannot fit the data on these eight items even when we allow for etiological heterogeneity. The pattern of endorsement probabilities associated with each of the four classes precludes a simple "unidimensional" model for the latent process underlying variation in symptom profile in this population. The extension of the approach to larger pedigrees and to linkage analysis is briefly considered.

Adolescent↗

PubMed1993

A test of the equal-environment assumption in twin studies of psychiatric illness.

The traditional twin method is predicated on the equal-environment assumption (EEA)--that monozygotic (MZ) and dizygotic (DZ) twins are equally correlated in their exposure to environmental events of etiologic importance for the trait under study. In 1968, Scarr proposed a test of the EEA which examines the impact of phenotypic similarity in twins of perceived versus true zygosity. We apply this test for the EEA to five common psychiatric disorders (major depression, generalized anxiety disorder, phobia, bulimia, and alcoholism), as assessed by personal interview, in 1030 female-female twin pairs from the Virginia Twin Registry with known zygosity. We use a newly developed model-fitting approach which treats perceived zygosity as a form of specified familial environment. In 158 of the 1030 pairs (15.3%), one or both twins disagreed with the project-assigned zygosity. Model fitting provided no evidence for a significant influence of perceived zygosity on twin resemblance for any of the five disorders. Although limited in power, these results support the validity of the EEA in twin studies of psychiatric disorders.

Adult↗

PubMed1993

Testing hypotheses about direction of causation using cross-sectional family data.

We review the conditions under which cross-sectional family data (e.g., data on twin pairs or adoptees and their adoptive and biological relatives) are informative about direction of causation. When two correlated traits have rather different modes of inheritance (e.g., family resemblance is determined largely by family background for one trait and by genetic factors for the other trait), cross-sectional family data will allow tests of strong unidirectional causal hypotheses (A and B are correlated "because of the causal influence of A on B" versus "because of the causal influence of B on A") and, under some conditions, also of the hypothesis of reciprocal causation. Possible sources of errors of inference are considered. Power analyses are reported which suggest that multiple indicator variables will be needed to ensure adequate power of rejecting false models in the presence of realistic levels of measurement error. These methods may prove useful in cases where conventional methods to establish causality, by intervention, by prospective study, or by measurement of instrumental variables, are unfeasible economically, ethically or practically.

Adoption↗

PubMed1993

Estimating and controlling for the effects of volunteer bias with pairs of relatives.

If pairs of relatives correlate in their liability to participate in a research project, it is possible to test for the effects of volunteering on the criterion variable of interest. Much of the information for this test comes from a difference in criterion variable mean between individuals with and those without a cooperative relative. Also, if data are available from more than one class of relative, it may be possible to discriminate between (i) volunteering that occurs as a consequence of the criterion variable and (ii) volunteering as a cause of the criterion. Likelihood formulae are presented that permit quantification and significance testing of volunteer bias. If data are collected from a genetically informative design such as a twin study, it is possible to estimate genetic and environmental parameters independent of the contaminating effects of such bias. We describe some methods of reducing the computational burden of multidimensional integration to allow extension to multivariate data. Implications for research design and management are discussed.

Adult↗

PubMed1993

Genetic contribution to risk of smoking initiation: comparisons across birth cohorts and across cultures.

Self-report data on smoking initiation (whether the respondent admitted ever having smoked) were obtained from three large adult twin samples (Australia, N = 3,808 pairs; Virginia, N = 2,145 pairs; AARP, N = 3,620 pairs). Data were broken down into birth cohorts, and genetic models were fitted to test whether the decline, in more recent birth cohorts, in the percentage of individuals becoming smokers has led to a change in the relative contributions of genes and environment to risk of becoming a smoker. Despite a marked change in the proportion of male respondents who reported ever having smoked, we found no evidence for cohort differences in genetic and environmental effects (no Genotype x Cohort interaction). Significant differences in genetic and environmental parameters were found between sexes, and between the Australian and the two U.S. samples. In the U.S. samples, estimates of the genetic contribution to risk of becoming a smoker were 60% in men, 51% in women. In the Australian sample, heritability estimates were 33% in men, but 67% in women. Significant shared environmental effects on smoking initiation also were found, accounting for 23% of the variance in U.S. men, 28% of the variance in U.S. women, 39% of the variance in Australian men, and 15% of the variance in Australian women. In models that allowed for the environmental impact of cotwin smoking on a twin's risk of smoking initiation, estimates of the direct genetic contribution to risk of smoking initiation were comparable or higher (49-58% in U.S. women and 71% in Australian women; 58-61% in U.S. men, and 37% in Australian men).

Adult↗

PubMed1993

Major depression and phobias: the genetic and environmental sources of comorbidity.

In a population based sample of 2163 personally interviewed female twins, substantial comorbidity was observed between DSM-III-R defined major depression (MD) and 4 subtypes of phobia: agoraphobia, social phobia, animal phobia and situational phobia. However, the level of comorbidity of MD with agoraphobia was much greater than that found with the other phobic subtypes. We concluded bivariate twin analyses to decompose the genetic and environmental sources of comorbidity between MD and the phobias. Our results suggest that a modest proportion of the genetic vulnerability to MD also influences the risk for all phobic subtypes, with the possible exception of situational phobias. Furthermore, the magnitude of comorbidity resulting from this shared genetic vulnerability is similar across the phobic subtypes. By contrast, the non-familial environmental experiences which predispose to depression substantially increase the vulnerability to agoraphobia, have a modest impact on the risk for social and situational phobias and no effect on the risk for animal phobias. The increased comorbidity between MD and agoraphobia results, nearly entirely, from individual-specific environmental risk factors for MD which also increase the risk for agoraphobia but not for other phobias.

Adult↗

PubMed1993

Panic disorder in women: a population-based twin study.

Previous studies based on probands from clinical samples suggest that panic disorder aggregates strongly in families and may be due to a highly penetrant single major locus. In this study we examine panic disorder as assessed at blind, structured psychiatric interview in 2163 women from a population-based twin registry. DSM-III-R diagnoses were assigned at a narrow and at a broad level both by clinician review and by computer algorithm. The familial aggregation of panic disorder in this sample was only modest. The relatively small number of affected individuals prevented a definitive resolution of competing genetic and non-genetic models of familial transmission. Although there was some inconsistency across diagnostic approaches, most results suggested that the familial aggregation of panic disorder was due largely to genetic factors. Using a multifactorial-threshold model, the best estimates of the heritability of liability ranged from 30 to 40%. From a familial perspective, panic disorder with phobic avoidance appears to represent a more severe form of the syndrome than panic disorder without avoidance. Our results, which suggest that in the general population panic disorder is only a moderately heritable condition, are at variance with results from several previous investigations based on clinically ascertained samples.

Adult↗

PubMed1993

Age-specific genetic effects for blood pressure.

Correlations between relatives were determined for systolic and diastolic blood pressure. The correlations decrease as age differences between relatives increase in a Norwegian sample with 43,751 parent-offspring pairs, 19,140 pairs of siblings, and 169 pairs of twins. A simple biometric model specifying only age-specific genetic additive effects and environmental effects fitted well to correlations between cotwins, pairs of siblings, and parent-offspring dyads in subsets of relatives grouped by age differences. None of the environmental effects appeared to be due to environmental factors that are shared by family members. Models that excluded a parameter for the age-specific genetic influence did not fit the data. The results may partly explain what seems to be a discrepancy between relatively low parent-offspring correlations from previous nuclear family studies and high correlations from twin studies, especially in identical twins.

Adult↗

PubMed1993

The prediction of major depression in women: toward an integrated etiologic model.

OBJECTIVE: The authors develop an exploratory, integrated etiologic model for the prediction of episodes of major depression in an epidemiologic sample of women. METHOD: Both members of 680 female-female twin pairs of known zygosity from a population-based register were assessed three times at greater than 1-year intervals. The last two assessments included a structured interview evaluation for presence of episodes of major depression, defined by DSM-III-R, in the preceding year. The final structural equation model contained nine predictor variables: genetic factors, parental warmth, childhood parental loss, lifetime traumas, neuroticism, social support, past depressive episodes, recent difficulties, and recent stressful life events. RESULTS: The best-fitting model predicted 50.1% of the variance in the liability to major depression. The strongest predictors of this liability were, in descending order, 1) stressful life events, 2) genetic factors, 3) previous history of major depression, and 4) neuroticism. While 60% of the effect of genetic factors on the liability to major depression was direct, the remaining 40% was indirect and mediated largely by a history of prior depressive episodes, stressful life events, lifetime traumas, and neuroticism. The model suggested that at least four major and interacting risk factor domains are needed to understand the etiology of major depression: traumatic experiences, genetic factors, temperament, and interpersonal relations. CONCLUSIONS: Major depression is a multifactorial disorder, and understanding its etiology will require the rigorous integration of genetic, temperamental, and environmental risk factors.

Adult↗

PubMed1992

A population-based twin study of alcoholism in women.

OBJECTIVE: To clarify the role of genetic factors in the etiology of alcoholism in women. DESIGN AND SETTING: Personal structured psychiatric interviews conducted by researchers "blinded" to the status of the co-twin in an epidemiologic sample of 1030 female-female twin pairs of known zygosity from the population-based Virginia Twin Registry. MEASURES: Three definitions of lifetime prevalence of alcoholism based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria: (1) alcoholism with tolerance or dependence; (2) alcoholism with or without tolerance-dependence; and (3) alcoholism with or without tolerance-dependence or problem drinking. RESULTS: Using narrow, intermediate, or broad definitions, the probandwise concordance for alcoholism was consistently higher in monozygotic than in dizygotic twin pairs. Multifactorial threshold models suggested that the heritability of liability to alcoholism in women is in the range of 50% to 60%. CONCLUSIONS: The results support the hypothesis that genetic factors play a major role in the etiology of alcoholism in women. Women should be well represented in the efforts currently under way to elucidate the molecular basis of the genetic susceptibility to alcoholism.

Alcoholism↗

PubMed1992

Childhood parental loss and adult psychopathology in women. A twin study perspective.

We examine the relationship between parental loss prior to age 17 years and adult psychopathology in 1018 pairs of female twins from a population-based registry. The relationship between loss and adult psychopathology varied as a function of the kind of loss (death vs separation), the parent involved, and the form of psychopathology. Increased risk for major depression and generalized anxiety disorder was associated with parental separation but not parental death and with separation from either mother or father. Panic disorder was associated with parental death and maternal, but not paternal, separation. Increased risk for phobia was associated with parental death and not parental separation. Risk for eating disorder was unrelated to the experience of parental loss. A model that includes parental loss as a form of "specified" family environment shows that, if it is truly an environmental risk factor for adult psychopathologic conditions, it can account for between 1.5% and 5.1% of the total variance in liability to these disorders and is responsible for between 7.0% and 20.5% of the tendency for these disorders to aggregate in siblings.

Adolescent↗

PubMed1992

A population-based twin study of major depression in women. The impact of varying definitions of illness.

Although depression aggregates in families, the degree to which this aggregation results from genetic vs environmental factors remains uncertain. We examined this question in 1033 female-female twin pairs from a population-based registry. Both members of each twin pair were "blindly" assessed by structured psychiatric interview. Nine commonly used definitions of major depression, which produced life-time prevalence rates ranging from 12% to 33%, were examined. For all definitions, the results of model fitting to twin correlations suggested that the liability to depression results from genetic factors and environmental experiences unique to the individual. For seven of the definitions, the estimated heritability of liability was similar, ranging from 33% to 45%. For the two definitions that included only primary cases of depression, the heritability was lower (21% to 24%). The results document that in women (1) genetic factors play a substantial, but not overwhelming, role in the cause of depression; (2) the tendency for depression to aggregate in families results largely from shared genetic and not from shared environmental factors; (3) except for definitions that exclude secondary cases, the magnitude of genetic influence is similar in broadly and narrowly defined forms of major depression; and (4) most environmental experiences of causative importance for depression are those not shared by members of an adult twin pair.

Adolescent↗

PubMed1992

Generalized anxiety disorder in women. A population-based twin study.

Little is known about the role of familial and genetic factors in the etiology of generalized anxiety disorder (GAD), a new disorder first proposed in DSM-III. We examine this question in 1033 female-female twin pairs from a population-based registry. Both members in each twin pair were "blindly" assessed by structured psychiatric interview. Our results suggest the following: (1) GAD is a moderately familial disorder; (2) the tendency for GAD to run in families seems to be due largely or entirely to genetic factors shared between relatives rather than to the effects of the familial environment; (3) the heritability of GAD, estimated at around 30%, is modest, with the remainder of the variance in liability resulting from environmental factors not shared by adult twins; (4) the heritability of GAD cannot be explained solely by the occurrence of GAD only during episodes of major depression or panic disorder; and (5) the etiologic role of genetic factors is probably similar in GAD with a 1- vs a 6-month minimum duration of illness.

Adult↗

PubMed1992

The genetic epidemiology of phobias in women. The interrelationship of agoraphobia, social phobia, situational phobia, and simple phobia.

In 2163 personally interviewed female twins from a population-based registry, the pattern of age at onset and comorbidity of the simple phobias (animal and situational)--early onset and low rates of comorbidity--differed significantly from that of agoraphobia--later onset and high rates of comorbidity. Consistent with an inherited "phobia proneness" but not a "social learning" model of phobias, the familial aggregation of any phobia, agoraphobia, social phobia, and animal phobia appeared to result from genetic and not from familial-environmental factors, with estimates of heritability of liability ranging from 30% to 40%. The best-fitting multivariate genetic model indicated the existence of genetic and individual-specific environmental etiologic factors common to all four phobia subtypes and others specific for each of the individual subtypes. This model suggested that (1) environmental experiences that predisposed to all phobias were most important for agoraphobia and social phobia and relatively unimportant for the simple phobias, (2) environmental experiences that uniquely predisposed to only one phobia subtype had a major impact on simple phobias, had a modest impact on social phobia, and were unimportant for agoraphobia, and (3) genetic factors that predisposed to all phobias were most important for animal phobia and least important for agoraphobia. Simple phobias appear to arise from the joint effect of a modest genetic vulnerability and phobia-specific traumatic events in childhood, while agoraphobia and, to a somewhat lesser extent, social phobia result from the combined effect of a slightly stronger genetic influence and nonspecific environmental experiences.

Adolescent↗

PubMed1992

Major depression and generalized anxiety disorder. Same genes, (partly) different environments?

Bivariate twin analysis can determine the extent to which two disorders share common genetic, familial environmental, or individual-specific environmental risk factors. We applied this method to lifetime diagnoses of major depression and generalized anxiety disorder as assessed at personal interview in a population-based sample of 1033 pairs of female same-sex twins. Three definitions of generalized anxiety disorder were used that varied in minimum duration (1 vs 6 months) and in the presence or absence of a diagnostic hierarchy. For all definitions of generalized anxiety disorder, the best-fitting twin model was the same. Familial environment played no role in the etiology of either condition. Genetic factors were important for both major depression and generalized anxiety disorder and were completely shared between the two disorders. A modest proportion of the nonfamilial environmental risk factors were shared between major depression and generalized anxiety disorder. Within the limits of our statistical power, our findings suggest that in women, the liability to major depression and generalized anxiety disorder is influenced by the same genetic factors, so that whether a vulnerable woman develops major depression or generalized anxiety disorder is a result of her environmental experiences.

Adult↗

PubMed1992

Genetic and environmental contributions to the variance of body height in a sample of first and second degree relatives.

Height was measured in a health screening of the population in Nord-Trøndelag, Norway. Correlations were computed for 24,281 pairs of spouses, 43,613 pairs of parents and offspring, 19,168 pairs of siblings, 1,318 pairs of grandparents and grandchildren, 1,218 cognate avuncular pairs, 849 noncognate avuncular pairs, 175 pairs of same-sexed twins, and smaller groups of other types of relatives. Fitting of structural equation models showed proportions of additive genetic variance of approximately 0.8 for both sexes and small sex-specific effects that probably reflect genetic dominance or environmental sibling effects. The correlations between parents and offspring were significantly lower in old than young cohorts, seeming to imply some kind of interaction effect between genes and environment.

Age Factors↗

PubMed1992

Genetic and environmental effects on blood pressure in a Norwegian sample.

Systolic (SBP) and diastolic (DBP) blood pressures were measured in a health screening of the adult population in Nord-Trøndelag, Norway. Correlations were computed for 23,936 pairs of spouses, 43,586 pairs of parent and offspring, 19,151 pairs of siblings, 1,251 pairs of grandparents-grandchildren, 1,146 pairs of biological uncles/aunts-nephews/nieces (avuncular), 801 non-biological avuncular pairs, 169 pairs of same-sex twins, and smaller groups of other types of relationships. Spouse correlations of 0.08 and 0.09 were approximately constant or slightly decreasing with marital duration. The correlation values for SBP and DBP were approximately 0.16 for parents-offspring, 0.19 to 0.23 for same-sex siblings with similar values for DZ twins, 0.19 and 0.16 for opposite-sex siblings, 0.52 and 0.43 for MZ twins, and close to zero for most of the second-order relationships. Genetic additive variance was estimated at 0.29 and genetic dominance variance at 0.18 with the best model for SBP. The corresponding estimates from the best models for DBP were 0.29 or lower and 0.22 or lower, the sum not exceeding 0.35. There was evidence of a moderate effect of environmental factors shared by same-sex siblings and twins (for DBP), but no cultural transmission, and whether or not adult relatives live together does not affect familial resemblance for BP. The data did not permit a very precise resolution of the relative magnitude of genetic dominance and sibling effects. The correlation structure did not show sex-specific genetic effects.

Adult↗

PubMed1992

The analysis of parental ratings of children's behavior using LISREL.

A common procedure for assessing children's behavior is to obtain parental ratings of the child. Since the ratings obtained are a function of both parent and child, disentangling the child's phenotype from that of the rater becomes an important methodological problem. For the analysis of genetic and environmental contributions to children's behavior, solutions to this are available when multiple raters, e.g., two parents, rate multiple children, e.g., twins. This paper describes and illustrates simple LISREL models for the analysis of parental ratings of children's behavior. We show how the assumption that mothers and fathers are rating the same behavior in children can be contrasted with the weaker alternative that parents are rating correlated behaviors. Given the stronger assumption, which appears adequate for ratings of children's internalizing behavior problems, the contribution of rater bias and unreliability may be separated from the shared and nonshared environmental components of variation in a behavior genetic analysis.

Adolescent↗