A twin study of psychomotor and physiological responses to an acute dose of alcohol

A battery of psychomotor tasks and physiological measures was administered to 206 pairs of twins before alcohol and then three times at hourly intervals after they ingested a standard dose of ethanol (0.75 g/kg body weight). Repeat measurements were obtained for 41 of these pairs on a second occasion. Performance on motor coordination, standing steadiness, pursuit rotor, arithmetic computation, and reaction-time tasks deteriorated after alcohol, but decrements on the five tasks were generally independent of each other. Measurements of blood pressure, pulse rate, and skin temperature were all elevated following alcohol intake, but these responses were also uncorrelated. The variance in many of these measures increased after alcohol. An analysis of covariance structure revealed that most of this additional variance exposed by alcohol was genetic in origin, particularly for standing steadiness, pursuit rotor, arithmetic computation, and pulse rate. Up to 50% of the variance in body sway after alcohol was estimated to be due to genetic factors expressed only under the influence of alcohol. Although significant correlations were found with blood alcohol concentration, previous drinking experience, and the personality trait Extraversion, little of the genetic variance exposed by alcohol could be explained by these predictors. It is concluded that the sources of the considerable genetic variation affecting performance under alcohol must be sought elsewhere.This work was supported by the Australian Associated Brewers.     

Association of the gastric alcohol dehydrogenase gene ADH7 with variation in alcohol metabolism

Seven alcohol-metabolizing enzymes are encoded by the human alcohol dehydrogenase (ADH) gene cluster on chromosome 4q22-23. One of these genes, ADH7, is uniquely expressed in the stomach mucosa and can influence metabolism of alcohol before its absorption into the blood. However, the contribution of ADH7 to the overall genetic variation in alcohol oxidation in vivo is unknown. Data on in vivo alcohol metabolism were obtained for 206 Australian twin pairs of Caucasian ancestry, following ingestion of a standard dose (0.75 g kg(-1) body weight) of alcohol. Twenty-five single nucleotide polymorphisms that cover the ADH7 encoding region were genotyped. The patterns of linkage disequilibrium among these SNPs identified a recombinational hotspot within intron 7 of the ADH7 gene. A model for the absorption and elimination of alcohol from the body led to the identification of haplotypes associated with inter-individual variation in the early stages of alcohol metabolism. These are within a 35 kb DNA tract contained in the region 5' of intron 7 in the ADH7 gene. The region accounts for 18% of the linkage for alcohol concentration associated with the ADH region, or approximately 11% of the genetic variance.     

Modeling Genetic and Environmental Factors to Increase Heritability and Ease the Identification of Candidate Genes for Birth Weight: A Twin Study

Heritability estimates of birth weight have been inconsistent. Possible explanations are heritability changes during gestational age or the influence of covariates (e.g. chorionicity). The aim of this study was to model birth weights of twins across gestational age and to quantify the genetic and environmental components. We intended to reduce the common environmental variance to increase heritability and thereby the chance of identifying candidate genes influencing the genetic variance of birth weight. Perinatal data were obtained from 4232 live-born twin pairs from the East Flanders Prospective Twin Survey, Belgium. Heritability of birth weights across gestational ages was estimated using a non-linear multivariate Gaussian regression with covariates in the means model and in covariance structure. Maternal, twin-specific, and placental factors were considered as covariates. Heritability of birth weight decreased during gestation from 25 to 42 weeks. However, adjusting for covariates increased the heritability over this time period, with the highest heritability for first-born twins of multipara with separate placentas, who were staying alive (from 52% at 25 weeks to 30% at 42 weeks). Twin-specific factors revealed latent genetic components, whereas placental factors explained common and unique environmental factors. The number of placentas and site of the insertion of the umbilical cord masked the effect of chorionicity. Modeling genetic and environmental factors leads to a better estimate of their role in growth during gestation. For birth weight, mainly environmental factors were explained, resulting in an increase of the heritability and thereby the chance of finding genes influencing birth weight in linkage and association studies. Edited by David Allison.     

Longitudinal Genetic Analysis of Problem Behaviors in Biologically Related and Unrelated Adoptees

The genetic and environmental influences on problem behaviors at two assessment points, three years apart, and their stability were studied in a sample of international adoptees, initially aged 10 to 15 years. Parents of 111 pairs of adopted biological siblings, 221 pairs of adopted nonbiological siblings and 1484 adopted singletons completed the Child Behavior Checklist (75 pairs, 154 pairs and 1080 singletons respectively at second assessment). At first assessment, genetic factors accounted for more than 50% of the variance in the Externalizing, Aggressive Behavior, Attention Problems and Social Problems scales. Shared environmental influences explained 40% of the variance in the Total Problem scale and less for all other scales. Nonshared environmental influences were most important for the Internalizing scale and its subscales, and for the Thought Problems and Delinquent Behavior scales. At the second assessment, genetic factors explained most of the variance in the Total Problem, Externalizing and Aggressive Behavior scales, while nonshared environmental influences explained most of the variance in all other scales. Shared environmental influences explained 33% of the variance in the Internalizing scale and less for the other scales. The stability of the Externalizing scale over time was caused mostly by genetic factors, while nonshared environmental factors mostly caused the stability of the Internalizing scale.     

Research advances in ethanol metabolism.

The pharmacokinetics of alcohol determines the time course of alcohol concentration in blood after the ingestion of an alcoholic beverage and the degree of exposure of organs to its effects. The interplay between the kinetics of absorption, distribution and elimination is thus important in determining the pharmacodynamic responses to alcohol. There is a large degree of variability in alcohol absorption, distribution and metabolism, as a result of both genetic and environmental factors. The between-individual variation in alcohol metabolic rates is, in part due to allelic variants of the genes encoding the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). This review summarizes recent developments in the investigation of the following influences on alcohol elimination rate: gender, body composition and lean body mass, liver volume, food and food composition, ethnicity, and genetic polymorphisms in alcohol metabolizing enzymes as well as in the promoter regions of the genes for these enzymes. Evaluation of the factors regulating the rates of alcohol and acetaldehyde metabolism, both genetic and environmental, will help not only to explain the risk for development of alcoholism, but also the risk for development of alcohol-related organ damage and developmental problems.     

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms.

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain.     

Adolescent alcohol use is a risk factor for adult alcohol and drug dependence: evidence from a twin design

BACKGROUND: Early alcohol use is associated with abuse and dependence of licit and illicit substances later in life. The role of genetic and environmental factors in this association is not conclusive. METHOD: In 1992, data on substance use, abuse/dependence and psychiatric disorders were collected from 8169 male twin members of the Vietnam Era Twin Registry. The interview obtained age of onset of regular drinking (one drink/month for 6 or more months). Regression analyses of twin pairs discordant for early alcohol use tested whether the association between early drinking (before age 17) and adult substance use and abuse/dependence remained after controlling for genetic factors, family environment and covariates. Twin models tested for common genetic and/or environmental influences on early drinking and adult alcohol dependence and ever use and abuse/dependence on marijuana and other drugs. RESULTS: Co-twin analyses suggested the association between early regular alcohol use and adult alcohol dependence, marijuana and other drug use, and marijuana and other drug abuse/dependence could not be entirely explained by common genetic and shared family environmental factors. Genetic contributions to early regular drinking were significantly correlated with those on use of marijuana (rA=0.59), use of other drugs (rA=0.64), alcohol dependence (rA=0.54) and abuse/dependence of marijuana and other drugs (rA=0.63 and 0.66). Small but significant unique environmental correlations (rE range 0.11-0.22) indicated that familial factors could not entirely explain the association between early alcohol use and later substance use, abuse and dependence. CONCLUSIONS: Early regular drinking is associated with later alcohol dependence and use, abuse/dependence on drugs. The association is not entirely explained by genetic or shared family environmental factors. This suggests unique environmental factors contribute to transitions from early regular alcohol drinking to use, abuse and dependence on alcohol and other substances.     

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:391–397, 1999. © 1999 Wiley-Liss, Inc.     

Genetic Correlation Between the P300 Event-Related Brain Potential and the EEG Power Spectrum

Previous studies have demonstrated moderate heritability of the P300 component of event-related brain potentials (ERPs) and high heritability of background electroencephalogram (EEG) power spectrum. However, it is unclear whether EEG and ERPs are influenced by common or independent genetic factors. This study examined phenotypic and genetic correlations between EEG spectral power and P300 amplitude using data from 206 Dutch twin pairs, age 16 years. Multivariate genetic models (Cholesky decomposition) were fitted to the observed twin covariances using Mx software. In males, genetic correlations between P300 and EEG power measures were high (0.54–0.74); 30% of the total P300 variance could be explained by genetic factors influencing EEG delta power and 26% by P300-specific genetic factors (total heritability 56%). In females, 45% of P300 variance could be attributed to familial influences that were shared with the EEG. However, it was not possible to distinguish between the genetic versus shared environmental factors, consistent with previous analysis of P300 in this sample (van Beijsterveldt et al., 1998). The results suggest that a substantial proportion of genetic influences on P300 amplitude can be explained by strong heritability of slow EEG rhythms contributing to P300.     

Genetically Informed Regression Analysis: Application to Aggression Prediction by Inattention and Hyperactivity in Children and Adults

We present a procedure to simultaneously fit a genetic covariance structure model and a regression model to multivariate data from mono- and dizygotic twin pairs to test for the prediction of a dependent trait by multiple correlated predictors. We applied the model to aggressive behavior as an outcome trait and investigated the prediction of aggression from inattention (InA) and hyperactivity (HA) in two age groups. Predictions were examined in twins with an average age of 10 years (11,345 pairs), and in adult twins with an average age of 30 years (7433 pairs). All phenotypes were assessed by the same, but age-appropriate, instruments in children and adults. Because of the different genetic architecture of aggression, InA and HA, a model was fitted to these data that specified additive and non-additive genetic factors (A and D) plus common and unique environmental (C and E) influences. Given appropriate identifying constraints, this ADCE model is identified in trivariate data. We obtained different results for the prediction of aggression in children, where HA was the more important predictor, and in adults, where InA was the more important predictor. In children, about 36% of the total aggression variance was explained by the genetic and environmental components of HA and InA. Most of this was explained by the genetic components of HA and InA, i.e., 29.7%, with 22.6% due to the genetic component of HA. In adults, about 21% of the aggression variance was explained. Most was this was again explained by the genetic components of InA and HA (16.2%), with 8.6% due to the genetic component of InA.

     

The Influence of Religion on Alcohol Use Initiation: Evidence for Genotype X Environment Interaction

We examined the possible role of religious upbringing as a mediator of the shared environmental influences and as a moderator of the genetic influences on the risk of alcohol use initiation in a large population-based sample of Dutch adolescent and young adult twins (1967 twin pairs). There was not a significant association between religious participation and alcohol use initiation among Dutch adolescents and young adults. We also hypothesized that the relative magnitude of the genetic influences on the risk of alcohol use initiation would be greater for those adolescents and young adults who were raised in a less religious environment compared to those adolescents and young adults who were raised in a more religious environment. We indeed found higher heritabilities for females without a religious upbringing compared to females with a religious upbringing. Genetic influences accounted for 40% of the variance in alcohol use initiation in nonreligious females, compared to 0% in religiously raised females. Shared environmental influences accounted for 54% of the variance for nonreligious females and 88% of the variance in religious females. For males, the genetic variance was also higher in the nonreligious group compared to the religious group, but this difference was not statistically significant. Whether or not they were raised religiously, the liability to alcohol use initiation in males was moderately influenced by genetic factors (30%) and substantially influenced by shared environmental factors (60%).     

Genetic and Environmental Influences on EEG Coherence

EEG coherence measures the covariation in electrical brain activity between two locations on the scalp and is used to study connectivity between cortical regions. The aim of this study was to determine the heritability of EEG coherence. Coherence was measured in a group of 213 16-yr-old twin pairs. By including male and female twin pairs in the sample, sex differences in genetic architecture were systematically examined. The EEG was obtained during quiet supine resting. Coherence was estimated for short and long distance combinations of electrode pairs along the anterior-posterior axis within a hemisphere for four frequency bands (delta, theta, alpha and beta). Averaged over all electrode combinations about 60% of the variance was explained by genetic factors for coherence in the theta, alpha and beta bands. For the delta band, the heritability was somewhat lower. No systematic sex differences in genetic architecture were found. All environmental influences were nonshared, i.e., unique factors including measurement error. Environmental factors shared by twin siblings did not influence variation in EEG coherence. These results suggest that individual differences in coherence form a potential candidate for (molecular) genetic studies on brain function.     

Stability of Genetic and Environmental Influences on P300 Amplitude: A Longitudinal Study in Adolescent Twins

This study examined the stability of genetic and environmental influences on individual differences in P300 amplitude during adolescence. The P300 component is an event-related brain potential (ERP) that has attracted much attention as a biological marker for disturbed cognitive processing in psychopathology. Understanding the genetics of this biological marker may contribute to understanding the genetics of the associated psychopathologies. In a group of 213 adolescent twin pairs, the P300 component was measured twice, the first time at age 16 and the second time 18 months later. A large part of the variance of the P300 amplitude could be explained by familial factors, with estimates ranging from 30% to 81%. Whether the familial resemblance was due to genetic or shared environmental factors depended on sex. For males, genetic factors explained familial resemblance in P300 amplitude, but for females such resemblance was likely due to shared environmental factors. The phenotypic stability of the P300 amplitude from 16 to 18 years was high in both sexes, and stability could be attributed largely to the same familial factors. There was no evidence that new familial influences emerged at age 18.     

Further evidence for a significant effect of fetal genes on variation in birth weight

The contribution of fetal and maternal genes to the variation in birth weight was estimated in a sample of 5 ,625 grandchildren of monozygotic and dizygotic twins. Fetal and maternal genetic effects were separated by comparing the covariance structure for offspring of daughters of twins with that for offspring of sons of twins. Only insignificant amounts (3.0%) of the total variance in birth weight could be accounted for by maternal genes, while fetal genes seemed to account for the major part (69.4%) of the variation. Environmental factors common to sibs could explain 8.6% and random environmental factors 19.0% of the total variance. The findings are consistent with the results of an earlier study of birth weight in the same population but differ from findings in other populations.     

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.     

Cohort differences in genetic and environmental influences on retrospective reports of conduct disorder among adult male twins

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 % Cl = 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.     

Genetics of educational attainment in Australian twins: Sex differences and secular changes

The relative effects of genetic and environmental factors in producing individual differences in educational achievement are compared across women and men and over birth cohorts. In a large sample of Australian twin pairs, the heritability of self-reported educational attainment did not vary among women and men born before and after 1950. In a “psychometric” model of twin resemblance, based on separate self-reports in 1981 and 1989, genetic factors explained 57% of the stable variance in educational achievement, while environmental factors shared by twins accounted for 24% of the variance. Corrections for phenotypic assortative mating for educational level, however, suggested that estimated common-environmental effects could be entirely explained by the correlation between additive genetic values for mates. Taking this into account, heritability of “true” educational attainment in Australia may be as high as 82% with the remaining variation being due to individual environments or experiences. Unlike previous studies in Scandinavian countries, results in Australia suggest that factors influencing educational success are comparable between women and men and for individuals born at different points during this century.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.     

Longitudinal Analyses of the Determinants of Drinking and of Drinking to Intoxication in Adolescent Twins

Genetic and environmental determinants of self-reported alcohol consumption were investigated in a sample of 2513 twin pairs who were first assessed at age 16 and were followed-up at age 17. At age 16, 77% of the sample was drinking, and 65% of drinkers reported drinking to intoxication. Both drinking and drinking to intoxication increased at the 1-year follow-up. Model fitting indicated that most of the variance in drinking initiation was due to shared environmental effects but that shared environmental effects were less important, and additive genetic effects were more important, in explaining frequency of drinking among subjects who had already initiated drinking. Similarly, shared environmental effects explained most of the variation in initiation of drinking to intoxication but were less important in explaining frequency of intoxication among subjects who had already initiated drinking to intoxication. The magnitude of genetic and environmental estimates for males and females did not differ significantly, but it was clear that either different genetic factors or different shared environmental factors were influencing males and females. For all drinking variables studied, shared environmental effects decreased from age 16 to age 17, while additive genetic effects increased from age 16 to age 17.     

Genetic variation of individual alpha frequency (IAF) and alpha power in a large adolescent twin sample.

To further clarify the mode of genetic transmission on individual alpha frequency (IAF) and alpha power, the extent to which individual differences in these alpha indices are influenced by genetic factors were examined in a large sample of adolescent twins (237 MZ, 282 DZ pairs; aged 16). EEG was measured at rest (eyes closed) from the right occipital site, and a second EEG recording for 50 twin pairs obtained approximately 3 months after the initial collection, enabled an estimation of measurement error. Analyses confirmed a strong genetic influence on both IAF (h(2)=0.81) and alpha power (h(2)=0.82), and there was little support for non-additive genetic (dominance) variance. A small but significant negative correlation (-0.18) was found between IAF and alpha power, but genetic influences on IAF and alpha power were largely independent. All non-genetic variance was due to unreliability, with no significant variance attributed to unique environmental factors. Relationships between the alpha and IQ indices were also explored but were generally either non-significant or very low. The findings confirm the high heritability for both IAF and alpha power, they further suggest that the mode of genetic transmission is due to additive genetic factors, that genetic influences on the underlying neural mechanisms of alpha frequency and power are largely specific, and that individual differences in alpha activity are influenced little by developmental plasticity and individual experiences.