Biomedical subjects

M C Neale

Publications and source records attributed to M C Neale.

At least 73 records · Page 4Linked to original sources

PubMed1998

Multivariate genetic analysis of the causes of temperance board registrations. In all Swedish male-male [correction of male-female] twin pairs born 1926-1949.

BACKGROUND: The Temperance Boards in Sweden registered individuals for three reasons: public drunkenness, driving under the influence of alcohol and committing a crime in connection with alcohol. We wanted to ascertain whether these three forms of alcohol-related problems result from similar or different genetic and environmental risk factors. METHOD: We conducted a trivariate twin analysis of these three causes of registration in all male-male [corrected] twin pairs of known zygosity born in Sweden, 1926-1949 (n = 5177 twin pairs). RESULTS: Prevalences of registration for public drunkenness, drink-driving and alcohol-related crime were, respectively, 9.0, 3.6 and 4.0%. The best-fitting model had one general genetic and one general familial-environmental factor with specific genetic risk factors for drink-driving and specific familial-environmental risk factors for alcohol-related crime. CONCLUSIONS: The three causes for alcohol registration in Sweden largely reflect the same genetic and environmental risk factors. Estimated heritabilities were similar for the three forms of registration. However, specific genetic risk factors exist for drink-driving and specific familial-environmental risk factors for alcohol-related crime. Genetic factors are somewhat less important and familial-environmental factors more important for public drunkenness than for drink-driving and alcohol related crime.

Alcoholic Intoxication↗

PubMed1998

Sex differences and non-additivity in the effects of genes on personality.

New large-sample data show that non-additive genetic effects, probably epistatic interactions between loci, and sex-limited gene expression are significant features of the genetic architecture of human personality as measured by questionnaire scales of extraversion and neuroticism. Three large data sets--new data on large samples (n = 20,554) of US twins, their spouses, parents, siblings and children, correlations for Australian twins (n = 7,532), and previously published twin data from Finland (n = 14,288)--are subjected to an integrated analysis to test alternative hypotheses about the genetic causes of family resemblance in personality. When allowance is made for differences in reliability of the scales, the combined data are consistent with the same model for variation. There are significant amounts of genetic non-additivity for both dimensions of personality. The evidence favours additive x additive epistatic interactions rather than dominance. In the case of neuroticism, there is especially strong evidence of sex differences in genetic architecture favouring a greater relative contribution of non-additive genetic effects in males. The data confirm previous claims to find no major contribution of the shared environment of twins and siblings to these dimensions of personality. Correlations between spouses are zero, and the correlations for very large samples of siblings and non-identical twins do not differ significantly.

Diseases in Twins↗

PubMed1997

Selecting a control group in studies of the familial coaggregation of two disorders: a quantitative genetics perspective.

We sought to compare four different definitions of control groups in studies of the coaggregation between two disorders (A and B) on: 1) their ability to detect valid familial coaggregation; 2) their liability to artifactual evidence for familial coaggregation; and 3) their robustness to the overselection of comorbid cases. Using a quantitative genetic model of transmission, we simulated sibling pairs with familial and nonfamilial sources of comorbidity. Four different definitions of controls were tested to predict disorder B in siblings of cases vs. controls: 1) unscreened controls included subjects with A or B as well as subjects with either A or B; 2) in the symmetrical selection method, controls included only subjects without A; 3) supernormal controls included only subjects without A or B; and 4) in the pure proband method, cases included subjects with A only, and controls included only subjects without A or B. In the absence of selection bias, 1) the unscreened control and the symmetrical selection methods did not yield spurious evidence for familial coaggregation and could detect familial coaggregation; 2) the supernormal controls yielded spurious evidence of familial coaggregation; and 3) the pure proband method sometimes yielded spurious evidence for negative familial coaggregation, and had limited power to detect familial coaggregation. However, the pure proband method was the only one unaffected by overselection of comorbid cases. In the absence of selection bias, both the unscreened control and the symmetrical selection methods are appropriate, and the robustness of the pure proband method to overselection of comorbid cases may be an interesting feature in studies using clinical samples. Moreover, quantitative genetics methods may offer important advantages in the study of familial coaggregation.

Anxiety Disorders↗

PubMed1997

Temperance board registration for alcohol abuse in a national sample of Swedish male twins, born 1902 to 1949.

BACKGROUND: Temperance boards were established in Sweden to register and follow up individuals who were seen in legal or medical settings with problems of alcohol abuse. These records, available in a large epidemiologic twin population, have provided an objective and validated measure of alcohol abuse. METHODS: We examined Swedish temperance board registrations from 1929 to 1974 (n = 2516 individual twins) in all male-male Swedish twin pairs of known zygosity from the population-based Swedish Twin Registry; these twin pairs were born from 1902 to 1949 (n = 8935 pairs). RESULTS: The lifetime prevalence and probandwise concordance rates for temperance board registrations were 13.2% and 47.9%, respectively, in monozygotic twins and 14.6% and 32.8%, respectively, in dizygotic twins. Model fitting suggested that genetic and familial-environmental risk factors accounted for 54% (95% confidence interval [CI], 47%-61%) and 14% (95% CI, 8%-19%) of the liability to temperance board registration, respectively; these estimates were stable across birth cohorts. High genetic liability was reflected by large numbers of temperance board registrations and registrations for criminal alcohol use. Elevated familial-environmental liability was indicated by an early age at first registration. CONCLUSIONS: Genetic factors are of major etiologic importance for alcohol abuse in men, while familial environmental factors play a significant but less important role. The etiologic importance of these factors has remained constant in Sweden for men who were born in the first half of the 20th century.

Adult↗

PubMed1997

Genetic and environmental factors in relative body weight and human adiposity.

We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent-offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent-offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.

Adoption↗

PubMed1997

The use of likelihood-based confidence intervals in genetic models.

This article describes the computation and relative merits of likelihood-based confidence intervals, compared to other measures of error in parameter estimates. Likelihood-based confidence intervals have the advantage of being asymmetric, which is often the case with structural equation models for genetically informative studies. We show how the package Mx provides confidence intervals for parameters and functions of parameters in the context of a simple additive genetic, common, and specific environment threshold model for binary data. Previously published contingency tables for major depression in adult female twins are used for illustration. The support for the model shows a marked skew as the additive genetic parameter is systematically varied from zero to one. The impact of allowing different prevalence rates in MZ vs. DZ twins is explored by fitting a model with separate threshold parameters and comparing the confidence intervals. Despite the improvement in fit of the different prevalence model, the confidence intervals on all parameters broaden, owing to their covariance.

Adult↗

PubMed1997

Genetics and developmental psychopathology: 1. Phenotypic assessment in the Virginia Twin Study of Adolescent Behavioral Development.

We introduce an overlapping cohort sequential longitudinal study of behavioral development and psychopathology in a representative sample of 1412 pairs of twins aged 8 through 16 years. Multiple phenotypic assessments involve a full psychiatric interview with each child and each parent, and supplementary parental, teacher, and child interview material and questionnaires. For the first wave of assessments, the numbers of reported DSM-III-R symptoms of Major Depressive Disorder (MDD), Separation Anxiety Disorder (SAD), Overanxious Disorder (OAD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), and Attention Deficit Hyperactivity Disorder (ADHD), assessed through interviews, confirm patterns of age and sex trends found in other epidemiological samples, but underscore their dependence on whether the child or the parent is the informant. Correlations across domains for symptoms reported by the same informant are often as large as correlations across informants for the same domain of symptoms. Factor analyses of these symptom counts, taking account of informant view and unreliability of assessment, show the high degree of correlation between SAD and OAD, between MDD and OAD, and between CD and ODD. ADHD symptoms are relatively independent of the other domains, but show moderate correlations with CD, ODD, and MDD. Factorially derived dimensional questionnaire scales, based on child, parental, and teacher reports, show patterns of relationship to symptom counts consistent with both convergent and discriminant validity as indices of liability to clinical symptoms. Across informants, questionnaire scales provide as good a prediction of symptoms as do clinical interviews. Multitrait-multimethod confirmatory factor analysis reveals the patterns of relationship between symptoms of psychiatric disorder in children taking due account of informant and unique sources of variance. Gender differences are consistent within the correlated clusters of ODD/CD and MDD/SAD/OAD, although there are disorder-specific age trends. There are large informant-specific influences on the reporting of symptoms in clinical interviews. Dimensional questionnaire scales provide a useful source of additional information. In subsequent analyses of genetic and environmental etiology of childhood psychopathology we must expect that results may differ by informant and method of assessment. Multivariate and developmental analyses that explore the sources of these differences will shed new light on the relationship between genetic and environmentally influenced vulnerability and the manifestation of psychopathology in specific circumstances.

Adolescent↗

PubMed1997

Genetics and developmental psychopathology: 2. The main effects of genes and environment on behavioral problems in the Virginia Twin Study of Adolescent Behavioral Development.

Little is known about the contribution of genetic and environmental factors to risk for juvenile psychopathology. The Virginia Twin Study of Adolescent Behavioral Development allows these contributions to be estimated. A population-based, unselected sample of 1412 Caucasian twin pairs aged 8-16 years was ascertained through Virginia schools. Assessment of the children involved semi-structured face-to-face interviews with both twins and both parents using the Child and Adolescent Psychiatric Assessment (CAPA). Self-report questionnaires were also completed by parents, children, and teachers. Measures assessed DSM-III-R symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Conduct Disorder, Oppositional Defiant Disorder, Overanxious Disorder, Separation Anxiety, and Depressive Disorder. Factorially derived questionnaire scales were also extracted. Scores were normalized and standardized by age and sex. Maximum likelihood methods were used to estimate contributions of additive and nonadditive genetic effects, the shared and unique environment, and sibling imitation or contrast effects. Estimates were tested for heterogeneity over sexes. Generally, monozygotic (MZ) twins correlated more highly than dizygotic (DZ) twins, parental ratings more than child ratings, and questionnaire scales more highly than interviews. DZ correlations were very low for measures of ADHD and DZ variances were greater than MZ variances for these variables. Correlations sometimes differed between sexes but those for boy-girl pairs were usually similar to those for like-sex pairs. Most of the measures showed small to moderate additive genetic effects and moderate to large effects of the unique individual environment. Measures of ADHD and related constructs showed marked sibling contrast effects. Some measures of oppositional behavior and conduct disorder showed shared environmental effects. There were marked sex differences in the genetic contribution to separation anxiety, otherwise similar genetic effects appear to be expressed in boys and girls. Effects of rater biases on the genetic analysis are considered. The study supports a widespread influence of genetic factors on risk to adolescent psychopathology and suggests that the contribution of different types of social influence may vary consistently across domains of measurement.

Adolescent↗

PubMed1997

Predictors of problem drinking and alcohol dependence in a population-based sample of female twins.

OBJECTIVE: To identify characteristics associated with problem drinking (PD) and alcohol dependence (AD) in women. METHOD: Subjects were 2,163 white women aged 17-55 from the population-based Virginia Twin Registry. Measures were selected from a clinical interview and questionnaires to reflect five domains associated with alcoholism in prior studies; demographic characteristics, personality, health, and personal and family history of psychopathology. Logistic and linear regression analyses were used to predict PD and DSM-III-R defined AD. RESULTS: Multiple regression models accounted for 19% of the variance in PD (significant predictors included: higher parental education-particularly among younger women, being the primary breadwinner, less frequent church attendance, higher scores on measures of neuroticism, extraversion and interpersonal dependency, history of major depression and social phobia, paternal PD and maternal treatment for emotional problems); 9% of the variance in diagnosis of AD (predicted by generalized anxiety, paternal depression and maternal PD); and 20% of the variance in number of symptoms of AD (predicted by the interaction of younger age and less-educated parents, higher neuroticism and mastery, lower optimism, generalized anxiety and agoraphobia, and maternal PD). CONCLUSIONS: Personality characteristics and parental psychopathology are important predictors of PD and AD independent of their effect on risk for affective and anxiety disorders. Many characteristics found to be associated with PD and AD in bivariate analyses were not significant when considered in the context of other predictors. Future studies of the etiology of alcoholism among women should simultaneously study measures from a variety of domains.

Adolescent↗

PubMed1996

The identification and validation of distinct depressive syndromes in a population-based sample of female twins.

BACKGROUND: Depression, a clinically heterogeneous syndrome, may also be etiologically heterogeneous. Using a prospective, epidemiologic, and genetically informative sample of adult female twins, we identify and validate a typology of depressive syndromes. METHODS: Latent class analysis was applied to 14 disaggregated DSM-III-R symptoms for major depression reported over the last year by members of 1029 female-female twin pairs. RESULTS: Seven classes were identified, of which 3 represented clinically significant depressive syndromes: (1) mild typical depression, (2) atypical depression, and (3) severe typical depression. Severe typical depression was characterized by comorbid anxiety and panic, long episodes, impairment, and help seeking. Atypical depression was similar in severity to mild typical depression, but was characterized by increased eating, hypersomnia, frequent, relatively short episodes, and a proclivity to obesity. Individuals with recurrent episodes tended to have the same syndrome on each occasion. The members of twin pairs concordant for depression had the same depressive syndrome more often than expected by chance and this resemblance was greater in monozygotic than in dizygotic pairs. CONCLUSION: In an epidemiologic sample of female twins, depression is not etiologically homogeneous, but is instead made up of several syndromes that are at least partially distinct from a clinical, longitudinal, and familial/genetic perspective.

Adult↗

PubMed1996

Multivariate multipoint linkage analysis of quantitative trait loci.

Resolution of the genetic components of complex disorders may require simultaneous analysis of the contribution of individual quantitative trait loci (QTLs) to multiple variables. A likelihood approach is used to illustrate how the complexities of multivariate data may be resolved with multipoint linkage analysis. Sibling pair data were simulated from a model in which two QTLs and trait-specific polygenic effects explained all the sibling resemblance within and between five variables. Multipoint linkage analysis was used to obtain individual pair probabilities of having zero, one, or two alleles identical by descent, and these probabilities were applied in a weighted maximum-likelihood fit function. The results were compared with those obtained using conventional linear structural equation modeling to estimate the contribution of latent genetic factors to the genetic covariance in the multiple measures. Both analyses were conducted using the Mx package. Relatively poor agreement was found between genetic factors defined in purely statistical terms by varimax rotation of the first two factors of the genetic covariance matrix and the structure obtained by fitting a model jointly to the phenotypic and the multipoint linkage data.

Animals↗

PubMed1996

Assortative mating for relative weight: genetic implications.

Most work on the genetics of relative weight has not considered the role of assortative mating, i.e., mate selection based on similarity between mates. We investigated the extent to which engaged men and women in an archival longitudinal database were similar to each other in relative body weight prior to marriage and cohabitation. After controlling for age, a small but statistically significant mate correlation was found for relative weight (r=.13, p=.023), indicating some assortative mating. Furthermore, we examined whether mate similarity in relative weight prior to marriage predicts survival of the marriage. No significant effects were found. In sum, these results are consistent with those of other studies in suggesting that there is a small but significant intermate correlation for relative weight. However, they are unique in showing that these results cannot be explained on the basis of (a) cohabitation, (b) age similarity, or (c) selective survival of marriages between couples more similar in relative weight. The implications of these findings for heritability studies, linkage studies, and the estimation of shared environmental effects are discussed.

Adult↗

PubMed1996

Mating assortment and the liability to substance abuse.

Assortative mating can exert a profound influence on the phenotypic composition of the population since it may result in an increase in the frequency of the genotypes associated with extreme phenotypes. Applied to the risk for a disorder such as substance abuse, this would mean a possibility for an increase in the risk and severity of the disorder in consecutive generations. This paper reviews the theoretical and empirical literature on mechanisms related to mate resemblance for the liability to substance abuse, sources and consequences of such resemblance, and suggests directions for further research.

Alcoholism↗

PubMed1996

Childhood parental loss and alcoholism in women: a causal analysis using a twin-family design.

Childhood parental loss may be an important risk factor for psychiatric illness in adulthood. While this association has been carefully examined for depression, little is known about the role of parental loss in predisposing to alcoholism. We examined an epidemiological sample of female twin pairs with the same history of continuity or disruption in parent-child relationships (N=1018 pairs; mean age 30 years), using a range of definitions of alcoholism. Childhood parental loss through separation, but not death, substantially increased the risk in adulthood for all definitions of alcoholism. Furthermore, both paternal and maternal alcoholism substantially increased the probability of parental separation from their children. Proposing a structural equation twin-family model that incorporates childhood parental loss as a specified environmental risk factor, we examined how much of the association between childhood parental loss and alcoholism was causal (i.e. mediated by environmental factors) v. non-causal (mediated by genetic factors, with parental loss serving as an index of parental genetic susceptibility to alcoholism). Both the causal and non-causal paths were significant for all definitions of alcoholism. However, the causal-environmental pathway consistently accounted for most of the association. While a significant proportion of the association is due to non-causal genetic mechanisms, childhood parental loss (or the familial discord that precedes or follows it) is probably a direct and significant environmental risk factor for the development of alcoholism in women.

Adult↗

PubMed1996

A longitudinal study of stressful life events assessed at interview with an epidemiological sample of adult twins: the basis of individual variation in event exposure.

This study investigates the basis of individual variation in exposure to stressful life events (SLEs). A population based sample of 547 MZ and 390 DZ female-female twin pairs, aged between 17 and 55 years, were surveyed by two structured interviews, separated by at least 1 year, that enquired about SLEs experienced during the preceding 12 months. Data were analysed with a model that resolves occasion specific ("random') versus enduring ("stable') influences on SLEs. The latter is partitioned into that due to genetic, familial environmental and unique environmental factors. We demonstrate that both random factors and stable individual differences underlie variation in self-reported exposure to SLEs. For most network events this stable variance makes a relatively small contribution to the total variance in SLEs exposure and is almost entirely due to genetic or familial environmental effects. Stable individual differences are more important determinants of personal SLEs, and these reflect both familial factors as well as previous experiences unshared by relatives.

Adolescent↗

PubMed1996

The independence of physical attractiveness and symptoms of depression in a female twin population.

The relationship between physical attractiveness and symptoms of depression was investigated in a general population simple of 1,100 female twins. Photographs were rated by 4 raters. Symptoms of depression were measured by the Depression sub-scale of the SCL-54, by a self-rating based on the DSM-III-R, and by an MD diagnosis based on a structured interview (SCID). No relationships between ratings of physical attractiveness and symptoms of depression were found.

Adolescent↗

PubMed1996

Inheritance of physical fitness in 10-yr-old twins and their parents.

This study focuses on the quantification of genetic and environmental sources of variation in physical fitness components in 105 10-yr-old twin pairs and their parents. Nine motor tests and six skinfold measures were administered. Motor tests can be divided into those that are performance-related: static strength, explosive strength, running speed, speed of limb movement, and balance; and those that are health-related: trunk strength, functional strength, maximum oxygen uptake, and flexibility. The significance and contribution of genetic and environmental factors to variation in physical fitness were tested with model fitting. Performance-related fitness characteristics were moderately to highly heritable. The heritability estimates were slightly higher for health-related fitness characteristics. For most variables a simple model including genetic and specific environmental factors fitted the observed phenotypic variance well. Common environmental factors explained a significant part of the variation in speed components and flexibility. Assortative mating was significant and positive for speed components, balance, trunk strength, and cardiorespiratory fitness, but negative for adiposity. Static strength, explosive strength, functional strength, and cardiorespiratory fitness showed evidence for reduced genetic transmission or dominance. The hypothesis that performance-related fitness characteristics are more determined by genetic factors than health-related fitness was not supported. At this prepubertal age, genetic factors have the predominant effect on fitness.

Adult↗

PubMed1996

The heritability of body mass index among an international sample of monozygotic twins reared apart.

BACKGROUND: Published heritability estimates (h2) for body mass index (BMI) range from as low as 0.05 to as high as 0.90. The purpose of this paper is to introduce new data to help narrow the range of plausible estimates. SUBJECTS: Subjects were 53 pairs (23 M; 30 F) of monozygotic twins reared apart (MZAs), whose mean BMI was 24.2 (SD = 4.7). BMI's were transformed to approximate normality via the Box-Cox transformation. Twin paris came from the Finnish Twin Cohort (17 pairs), a data base of Japanese twins (10 pairs) and published case histories of primarily American twins (26 pairs). RESULTS: The h2 for MZAs is given by the correlation among the twin pairs. For the transformed data, the zero-order correlation of twins' BMIs was 0.79 for all twins, 0.63 for the Finnish twins, 0.73 for the Japanese twins and 0.85 for the 'archival' twins. When modeled with regression to control for relevant covariates, the estimate of h2 is either 0.50 or 0.70, depending on one's definition. The semipartial r was 0.50, suggesting that 50% of the total variance in BMI appears to the genetic in origin after controlling the covariates. The partial r was 0.70, suggesting that 70% of the variance in BMI that is not accounted for by the covariates can be attributed to genetic variation. Separation age had a small positive correlation with absolute intra-pair difference in BMI, suggesting that these estimates of h2 are not biased upwards due to early shared environment. CONCLUSIONS: Findings are consistent with past studies of MZAs and suggest that h2 estimates between 0.50 and 0.70 are reasonable. Implications of this finding are discussed.

Adult↗