Biomedical subjects

M C Neale

Publications and source records attributed to M C Neale.

At least 37 records · Page 2Linked to original sources

PubMed2001

Are smarter brains running faster? Heritability of alpha peak frequency, IQ, and their interrelation.

It has often been proposed that faster central nervous system (CNS) processing amounts to a smarter brain. One way to index speed of CNS processing is through the assessment of brain oscillations via electroencephalogram (EEG) recordings. The dominant frequency (peak frequency) with which neuronal feedback loops in an adult human brain oscillate in a relaxed state is around 10 cycles/sec, but large individual differences exist in peak frequencies. Earlier studies have found high peak frequencies to be associated with higher intelligence. In the present study, data from 271 extended twin families (688 participants) were collected as part of a large, ongoing project on the genetics of adult brain function and cognition. IQ was assessed with the Dutch version of the Wechsler Adult Intelligence Scale (WAIS-IIIR), from which four dimensions were calculated (verbal comprehension, working memory, perceptual organization, and processing speed). Individual peak frequencies were picked according to the method described by Klimesch (1999) and averaged 9.9 Hz (SD 1.01). Structural equation modeling indicated that both peak frequency and the dimensions of IQ were highly heritable (range, 66% to 83%). A large part of the genetic variance in alpha peak frequency as well as in working memory and processing speed was due to nonadditive factors. There was no evidence of a genetic correlation between alpha peak frequency and any of the four WAIS dimensions: Smarter brains do not seem to run faster.

Adult↗

PubMed2001

A review and meta-analysis of the genetic epidemiology of anxiety disorders.

OBJECTIVE: The authors conducted meta-analyses of data from family and twin studies of panic disorder, generalized anxiety disorder, phobias, and obsessive-compulsive disorder (OCD) to explore the roles of genetic and environmental factors in their etiology. METHOD: MEDLINE searches were performed to identify potential primary studies of these disorders. Data from studies that met inclusion criteria were incorporated into meta-analyses that estimated summary statistics of aggregate familial risk and heritability for each disorder. RESULTS: For family studies, odds ratios predicting association of illness in first-degree relatives with affection status of the proband (disorder present or absent) were homogeneous across studies for all disorders. The calculated summary odds ratios ranged from 4 to 6, depending on the disorder. Only for panic disorder and generalized anxiety disorder could the authors identify more than one large-scale twin study for meta-analysis. These yielded heritabilities of 0.43 for panic disorder and 0.32 for generalized anxiety disorder. For panic disorder, the remaining variance in liability could be attributed primarily to nonshared environment. For generalized anxiety disorder, this was true for men, but for women, a potentially significant role for common familial environment was also seen. CONCLUSIONS: Panic disorder, generalized anxiety disorder, phobias, and OCD all have significant familial aggregation. For panic disorder, generalized anxiety disorder, and probably phobias, genes largely explain this familial aggregation; the role of family environment in generalized anxiety disorder is uncertain. The role of nonshared environmental experience is significant, underscoring the importance of identifying putative environmental risk factors that predispose individuals to anxiety.

Anxiety Disorders↗

PubMed2000

Haplotypes of four novel single nucleotide polymorphisms in the nicotinic acetylcholine receptor beta2-subunit (CHRNB2) gene show no association with smoking initiation or nicotine dependence.

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.

DNA↗

PubMed2000

Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins.

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.

Adult↗

PubMed2000

ApoE polymorphism accounts for only part of the genetic variation in quantitative ApoE levels.

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.

Adolescent↗

PubMed2000

A study of the genetic and environmental etiology of stuttering in a selected twin sample.

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.

Adolescent↗

PubMed2000

Multivariate genetic analysis of brain structure in an extended twin design.

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.

Adult↗

PubMed2000

The relation between risk factors for binge eating and bulimia nervosa: a population-based female twin study.

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.

Adult↗

PubMed2000

A twin study of inattentive, aggressive, and anxious/depressed behaviors.

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.

Aggression↗

PubMed2000

Does intra-uterine growth discordance predict differential risk for adult psychiatric disorder in a population-based sample of monozygotic twins?

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.

Adult↗

PubMed2000

Genetic epidemiology of major depression: review and meta-analysis.

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 to additive genetic effects (point estimate of heritability of liability=37%, 95% CI=31%-42%), with a minimal contribution of environmental effects common to siblings (point estimate=0%, 95% CI=0%-5%), and substantial individual-specific environmental effects/measurement error (point estimate=63%, 95% CI=58%-67%). The literature suggests that recurrence best predicts the familial aggregation of major depression. CONCLUSIONS: Major depression is a familial disorder, and its familiality mostly or entirely results from genetic influences. Environmental influences specific to an individual are also etiologically significant. Major depression is a complex disorder that does not result from either genetic or environmental influences alone but rather from both. These findings are notably consistent across samples and methods and are likely to be generally applicable.

Adoption↗

PubMed2000

A multidimensional twin study of mental health in women.

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% to 49%. Family environment was an important influence on interpersonal relationships, substance use, and social support. CONCLUSIONS: Mental health is a complex phenotype that is influenced by a diverse array of genetic and environmental factors. 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.

Adult↗

PubMed2000

Structured latent growth curves for twin data.

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, all three components of growth appear strongly familial with the majority of variance associated with the shared environment; differences between the models were not great. Occasion-specific 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.

Algorithms↗

PubMed1999

Bivariate genetic analysis of fasting insulin and glucose levels.

The main aim of this study was to estimate the relative influence of genes and environment on fasting insulin levels, which were considered a proxy of insulin resistance. Possible sex differences in genetic and environmental influences, and the origin of the covariance between fasting insulin and glucose were investigated. Subjects were 209 pairs of middle-aged twins, divided into 5 sex-by-zygosity groups. A general bivariate model and a reciprocal causation model including fasting insulin and glucose were used in the analyses. For both quantitative genetic models, a model specifying additive genetic and unique environmental factors, which were the same in males and females, showed the best fit to the data. Heritability estimates were modest and highly similar in both models: 20-25% of the variance in fasting insulin, and around 50% of the variance in fasting glucose levels could be attributed to genetic factors. The two models could not be discriminated on the basis of their fit to the data. A submodel of the general bivariate model suggested that the covariance between glucose and insulin has a unique environmental basis, whereas for the reciprocal causation model both causal paths were needed to explain the phenotypic correlation between insulin and glucose and estimates of the reciprocal paths were of opposite sign, an indication for the expected negative feedback loop.

Adult↗

PubMed1999

A population-based twin study in women of smoking initiation and nicotine dependence.

BACKGROUND: The development of drug dependence requires prior initiation. What is the relationship between the risk factors for initiation and dependence? METHODS: Using smoking as a model addiction, we assessed smoking initiation (SI) and nicotine dependence (ND) by personal interview in 1898 female twins from the population-based Virginia Twin Registry. We developed a twin structural equation model that estimates the correlation between the liability to SI and the liability to ND, given SI. RESULTS: The liabilities to SI and ND were substantially correlated but not identical. Heritable factors played an important aetiological role in SI and in ND. While the majority of genetic risk factors for ND were shared with SI, a distinct set of familial factors, which were probably partly genetic, solely influenced the risk for ND. SI was associated with low levels of education and religiosity, high levels of neuroticism and extroversion and a history of a wide range of psychiatric disorders. ND was associated with low levels of education, extroversion, mastery, and self-esteem, high levels of neuroticism and dependency and a history of mood and alcohol use disorders. CONCLUSIONS: The aetiological factors that influence SI and ND, while overlapping, are not perfectly correlated. One set of genetic factors plays a significant aetiological role in both SI and ND, while another set of familial factors, probably in part genetic, solely influences ND. Some risk factors for SI and ND impact similarly on both stages, some act at only one stage and others impact differently and even in opposite directions at the two stages. The pathway to substance dependence is complex and involves multiple genetic and environmental risk factors.

Adult↗

PubMed1999

The structure of genetic and environmental risk factors for three measures of disordered eating.

BACKGROUND: The study explored the genetic and environmental risk factors for both the behaviours and attitudes characteristic of disordered eating. METHODS: In three waves of data collection, information was collected from female twins regarding their eating and attitudes towards eating, weight and shape. The first assessment consisted of a self-report questionnaire (1988-9) with 1682 women. The second assessment consisted of a semi-structured psychiatric interview schedule (1992-3), completed by 1852 women, many of whom had completed Wave 1 assessment. The third assessment, with 325 women chosen from Waves 1 and 2 (1995-6), consisted of a semi-structured interview (the Eating Disorder Examination). RESULTS: As only one twin pair was concordant for lifetime bulimia nervosa at Wave 3 assessment, ordinal measures of all assessments were used in a multivariate genetic analysis. Results indicated that additive genetic and non-shared environmental influences best explained variance in liability to disordered eating, with about 60% (95% CI 50-68) of the variance explained by genetic factors. Comparison with a model allowing for the effects of shared environment indicated genetic factors accounted for a similar degree of variance (59%, 95% CI 36-68). CONCLUSION: Liability to the development of the behaviours and attitudes characteristic of eating disorders is best explained by both environmental and genetic factors, with covariation between the three measures best explained by a single latent phenotype of disordered eating which has a heritability of 60%.

Adult↗

PubMed1999

A genetic analysis of the eating and attitudes associated with bulimia nervosa: dealing with the problem of ascertainment in twin studies.

Little is known about the etiology of bulimia nervosa and the attitudes associated with it. We have undertaken a study of selected (45 pairs) and unselected (106 pairs) female twins to elucidate the broad causes of individual differences in these behaviours and attitudes. The selected sample was chosen on the basis of at least one of the twin pair having a lifetime incidence of bulimia nervosa. Biometrical model fitting, which corrected for the biased twin correlations of the ascertained group, was used to investigate the genetic and environmental risk factors contributing to the development of bulimia nervosa. The best-fitting model showed that individual variation was best explained by additive genetic influences (62%) and nonshared environmental influences (38%). The proportion of genetic variance affecting individual variation in the ascertained group and the random group was not found to be significantly different. In summary, it is suggested that it may not be necessary to supplement a randomly selected sample with an ascertained sample when investigating the liability to a low-prevalence psychiatric disorder if a continuous measure of that disorder is available.

Adult↗

PubMed1999

The genetics of smoking initiation and quantity smoked in Dutch adolescent and young adult twins.

Not much is known about the genetic and environmental determinants of various aspects of substance use in adolescents. This study examined whether the inheritance of initiation of tobacco use in adolescents is independent of the inheritance of the number of cigarettes smoked. Alternative multifactorial threshold models were applied to data on tobacco use in 1676 Dutch adolescent twin pairs. The three models that were considered are (i) the single liability dimension model, (ii) the independent liability dimension model, and (iii) the combined model (CM). The results showed that there is not one underlying continuum of liability to smoking. The CM was the best-fitting model. This model postulates that there are separate initiation and quantity dimensions but allows for the possibility that there are some individuals who are so low on the liability to level of consumption that they are not using tobacco. There were no differences between males and females in the magnitude of the genetic and environmental influences on individual differences in smoking initiation and quantity smoked. Smoking initiation was influenced by genetic factors (39%) and shared environmental influences (54%). Once smoking is initiated genetic factors determine to a large extent (86%) the quantity that is smoked.

Adolescent↗