The endocannabinoid system has been implicated in stress adaptation and the regulation of mood in rodent studies, but few human association studies have examined these links and replications are limited.
To examine whether a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood physical abuse on lifetime anhedonia and depression and further, to replicate this interaction in an independent sample.
Genetic association study in 1041 young adult U.S. women with replication in an independent Australian sample of 1428 heroin dependent cases and 506 neighborhood controls.
Main outcome measure
Self-reported anhedonia and depression (with anhedonia).
In both samples, those who experienced childhood physical abuse were considerably more likely to report lifetime anhedonia. However, in those with one or more copies of the minor allele of rs1049353, this pathogenic effect of childhood physical abuse was attenuated. Thus, in those reporting childhood physical abuse, while 57% of those homozygous for the major allele reported anhedonia, only 29% of those who were carriers of the minor allele reported it (p < 0.02). rs1049353 also buffered the effects of childhood physical abuse on major depressive disorder, however this influence was largely attributable to anhedonic depression. These effects were also noted in an independent sample, where minor allele carriers were at decreased risk for anhedonia even when exposed to physical abuse.
Consistent with preclinical findings, a synonymous CNR1 polymorphism, rs1049353, is linked to the effects of stress attributable to childhood physical abuse on anhedonia and anhedonic depression. This polymorphism reportedly resides in the neighborhood of an exon splice enhancer and hence, future studies should carefully examine its impact on expression and conformational variation in CNR1, particularly in relation to stress adaptation.
CNR1; endocannabinoid; physical abuse; rs1049353; GxE; anhedonia; major depression
While there is solid evidence that cannabis use is heritable, attempts to identify genetic influences at the molecular level have yielded mixed results. Here, a large twin family sample (N=7452) was used to test for association between ten previously reported candidate genes and lifetime frequency of cannabis use using a gene-based association test. None of the candidate genes reached even nominal significance (p<.05). The lack of replication may point to our limited understanding of the neurobiology of cannabis involvement and also to potential publication bias and false-positive findings in previous studies.
genes; cannabis; genetics; association
We sought to determine whether parenting, sibling and peer influences are associated with offspring ever smoking, regular smoking and nicotine dependence (ND) after controlling for familial factors. We used a twin-family design and data from structured diagnostic surveys of 1,919 biological offspring (age 12–32 years), 1,107 twin fathers, and 1,023 mothers. Offspring were classified into one of four familial risk groups based on twin fathers' and their co-twins' history of DSM-III-R nicotine dependence. Multivariate multinomial logistic regression was used to model familial risk, paternal and maternal parenting behavior and substance use, sibling substance use, and friend and school peer smoking, alcohol and drug use. Ever smoking was associated with increasing offspring age, white race, high maternal pressure to succeed in school, sibling drug use, and friend smoking, alcohol and drug use. Offspring regular smoking was associated with these same factors with additional contribution from maternal ND. Offspring ND was associated with increasing offspring age, male gender, biological parents divorce, high genetic risk from father and mother ND, maternal problem drinking, maternal rule inconsistency and sibling drug use, and friend smoking, alcohol and drug use. Friend smoking had the largest magnitude of association with offspring smoking. This effect remains after accounting for familial liability and numerous parent and sibling level effects. Smoking interventions may have greatest impact by targeting smoking prevention among peer groups in adolescent and young adult populations.
smoking; nicotine dependence; peers; gene and environment
Earlier studies have found an elevated risk for psychopathology and suicidal behavior associated with childhood sexual abuse (CSA); however the degree to which risk is mediated by depression and post-traumatic stress disorder (PTSD) in women and men remains unclear. We examined these issues in data from a family study of childhood maltreatment (N=2559). We found significant CSA-associated risk for depression, PTSD, and suicidal behavior for women and men. In survival analyses controlling for these disorders, we observed persistent, but somewhat reduced, CSA-associated risk for suicidal ideation and suicide attempt. Our findings thus suggest these disorders partially mediate CSA-associated risk.
While most individuals initiate their use of tobacco prior to onset of cannabis use, recent reports have identified a smaller subset of youth who report onset of cannabis use prior to tobacco use. In this study, we characterize patterns of cannabis and tobacco use (tobacco but not cannabis, cannabis but not tobacco or both) and compare the factors associated with onset of tobacco before cannabis and cannabis before tobacco.
Data on 1812 offspring aged 12–32 years, drawn from two related offspring of Vietnam Era twin studies, were used. Individuals were divided into tobacco but not cannabis (T), cannabis but not tobacco (C) and users of both substances (CT). Those who used both could be further classified by the timing of onset of tobacco and cannabis use. Multinomial logistic regression was used to characterize the groups using socio-demographic and psychiatric covariates. Furthermore, data on parental smoking and drug use was used to identify whether certain groups represented greater genetic or environmental vulnerability.
22% (n=398) reported T, 3% (n=55) reported C and 44% reported CT (n=801). Of the 801 CT individuals, 72.8% (n=583), 9.9% (n=77) and 17.3% (n=139) reported onset of tobacco before cannabis, cannabis before tobacco and onsets at the same age. C users were as likely as CT users to report peer drug use and psychopathology, such as conduct problems while CT was associated with increased tobacco use relative to T. Onset of tobacco prior to cannabis, when compared onset of cannabis before tobacco or reporting initiation at the same age was associated with greater cigarettes smoked per day, however no distinct factors distinguished the group with onset of cannabis before tobacco from those with initiation at the same age.
A small subset of individuals report cannabis without tobacco use. Of those who use both cannabis and tobacco, a small group report cannabis use prior to tobacco use. Follow-up analyses that chart the trajectories of these individuals will be required to delineate their course of substance involvement.
Cannabis; Tobacco; Reverse Gateways
Serum butyrylcholinesterase (BCHE) activity is associated with obesity, blood pressure and biomarkers of cardiovascular and diabetes risk. We have conducted a genome-wide association scan to discover genetic variants affecting BCHE activity, and to clarify whether the associations between BCHE activity and cardiometabolic risk factors are caused by variation in BCHE or whether BCHE variation is secondary to the metabolic abnormalities. We measured serum BCHE in adolescents and adults from three cohorts of Australian twin and family studies. The genotypes from ∼2.4 million single-nucleotide polymorphisms (SNPs) were available in 8791 participants with BCHE measurements. We detected significant associations with BCHE activity at three independent groups of SNPs at the BCHE locus (P = 5.8 × 10−262, 7.8 × 10−47, 2.9 × 10−12) and at four other loci: RNPEP (P = 9.4 × 10−16), RAPH1-ABI2 (P = 4.1 × 10−18), UGT1A1 (P = 4.0 × 10−8) and an intergenic region on chromosome 8 (P = 1.4 × 10−8). These loci affecting BCHE activity were not associated with metabolic risk factors. On the other hand, SNPs in genes previously associated with metabolic risk had effects on BCHE activity more often than can be explained by chance. In particular, SNPs within FTO and GCKR were associated with BCHE activity, but their effects were partly mediated by body mass index and triglycerides, respectively. We conclude that variation in BCHE activity is due to multiple variants across the spectrum from uncommon/large effect to common/small effect, and partly results from (rather than causes) metabolic abnormalities.
Polysaccharide sidechains attached to proteins play important roles in cell–cell and receptor–ligand interactions. Variation in the carbohydrate component has been extensively studied for the iron transport protein transferrin, because serum levels of the transferrin isoforms asialotransferrin + disialotransferrin (carbohydrate-deficient transferrin, CDT) are used as biomarkers of excessive alcohol intake. We conducted a genome-wide association study to assess whether genetic factors affect CDT concentration in serum. CDT was measured in three population-based studies: one in Switzerland (CoLaus study, n = 5181) and two in Australia (n = 1509, n = 775). The first cohort was used as the discovery panel and the latter ones served as replication. Genome-wide single-nucleotide polymorphism (SNP) typing data were used to identify loci with significant associations with CDT as a percentage of total transferrin (CDT%). The top three SNPs in the discovery panel (rs2749097 near PGM1 on chromosome 1, and missense polymorphisms rs1049296, rs1799899 in TF on chromosome 3) were successfully replicated , yielding genome-wide significant combined association with CDT% (P = 1.9 × 10−9, 4 × 10−39, 5.5 × 10−43, respectively) and explain 5.8% of the variation in CDT%. These allelic effects are postulated to be caused by variation in availability of glucose-1-phosphate as a precursor of the glycan (PGM1), and variation in transferrin (TF) structure.
Given the weight placed on retrospective reports of age at first drink in studies of later drinking-related outcomes, it is critical that its reliability be established and possible sources of systematic bias be identified. The overall aim of the current study is to explore the possibility that the estimated magnitude of association between early age at first drink and problem alcohol use may be inflated in studies using retrospectively reported age at alcohol use onset.
The sample was comprised of 1,716 participants in the Missouri Adolescent Female Twin Study who reported an age at first drink in at least 2 waves of data collection (an average of 4 years apart). Difference in reported age at first drink at Time 2 vs. Time 1 was categorized as 2 or more years younger, within 1 year (consistent), or 2 or more years older. The strength of the association between age at first drink and peak frequency of heavy episodic drinking (HED) at Time 1 was compared with that at Time 2. The association between reporting pattern and peak frequency of HED was also examined.
A strong association between age at first drink and HED was found for both reports, but it was significantly greater at Time 2. Just over one-third of participants had a 2 year or greater difference in reported ageat first drink. The majority of inconsistent reporters gave an older age at Time 2 and individuals with this pattern of reporting engaged in HED less frequently than consistent reporters.
The low rate of HED in individuals reporting an older age at first drink at Time 2 suggests that the upward shift in reported age at first drink among early initiates is most pronounced for light drinkers. Heavy drinkers may therefore be overrepresented among early onset users in retrospective studies, leading to inflated estimates of the association between early age at initiation and alcohol misuse.
age at first drink; heavy episodic drinking; reporting bias
The objective of this study was to examine the underlying factorial architecture of lifetime DSM-IV alcohol use disorder (AUD) criteria in a population-based sample of adolescent and emerging adult female twins who had ever used alcohol (n=2832; aged 18-25 years), and to determine whether thresholds and factor loadings differed by age. Item response modeling was applied to DSM-IV AUD criteria. Compound criteria (e.g., persistent desire or unsuccessful attempts to quit or cut down) were included as separate items. Of the remaining 16 items, tolerance and use despite physical problems were the most and least commonly endorsed items, respectively. Underlying the items was a single factor representing liability to AUDs. Factor loadings ranged from 0.67 for blackouts to 0.90 for time spent using/recovering from effects. Some items assessing different DSM-IV criteria had very similar measurement characteristics, while others assessing the same criterion showed markedly different thresholds and factor loadings. Compared to that of women aged 21-25 years, the threshold for hazardous use was higher in women aged 18-20 years, but lower for used longer than intended and persistent desire to cut down. After accounting for threshold differences, no variations in discrimination across age groups were observed. In agreement with the extant literature, our findings indicate that the factorial structure of AUD is unidimensional, with no support for the abuse/dependence distinction. Individual components of compound criteria may differ in measurement properties; therefore pooling information from such divergent items will reduce information about the AUD construct.
alcohol use disorder; item response modeling; twins
Excessive alcohol consumption contributes to significant morbidity and mortality. Heritable influences contribute to 50% of the variation in alcohol consumption, suggesting the important role of genes. We used data on a previously defined alcohol consumption factor score in a sample of 827 young women to investigate association with 1014 single nucleotide polymorphisms in genes related to addiction.
Data were drawn from the Missouri Adolescent Female Twin Study (MOAFTS) with replication in the College Drinking Sample (CDS). Genotypic and phenotypic data were available on 827 MOAFTS and 100 CDS women of European- American ancestry. Data on 1014 SNPs across 130 genes related to addiction were utilized. Association was conducted in QTDT, which allows for identity-by-descent information to account accurately for twin status in the analysis. The total association variance components model was used, with specification of variance components for relatedness in MOAFTS.
The top signals included clusters of SNPs in TPH2 (e.g. rs1386496, p=0.0003) and DDC (e.g. rs3779084, p=0.0008), genes that encode proteins responsible for serotonin synthesis. Additional polymorphisms in ADH1B, ADH1C, ADH7 and ADH1A1 were also associated at p < 0.05. The FDR for the top signal (p=0.0003) was 0.15 suggesting nominal significance only. Replication was limited and noted for 2 SNPs in ADH1C.
While no results survive the burden of multiple testing, nominal findings in TPH2 and DDC suggest the potential role of the serotonin synthesis pathway in alcohol consumption.
The aim of the current study was to test the independent and joint contributions of 8 different types of trauma to posttraumatic stress disorder (PTSD) risk using data from a young adult female cohort. Associations of traumatic events with PTSD onset were examined using Cox proportional hazards models. Differences in risk as a function of age at trauma were tested. Childhood sexual assault, physical abuse, and neglect were stronger predictors of PTSD onset than adolescent/early adult occurrence of these events in individual models. In a model including all traumatic events, differential risk by age remained for sexual assault and physical abuse. Early sexual assault was the strongest predictor of risk but additional traumatic events increased risk even in its presence.
Little is known about the relationship between relative body weight and transition from experimentation to regular smoking in young adult women. In the current study, data from 2494 participants in wave 4 of the Missouri Adolescent Female Twin Study (aged 18-29 years) who reported ever smoking a cigarette were analyzed using logistic regression. Body mass index (BMI) at time of interview was categorized according to CDC adult guidelines, and regular smoking was defined as having ever smoked 100 or more cigarettes and having smoked at least once a week for two months in a row. Since the OR’s for the overweight and obese groups did not differ significantly from one another in any model tested, these groups were combined. Forty-five percent of women who had ever smoked had become regular smokers. Testing of interactions between potential covariates and levels of the categorical BMI variable revealed a significant interaction between overweight/obesity and childhood sexual abuse (CSA; p<0.001) associated with regular smoking. Among women reporting CSA, the association between overweight/obesity and having become a regular smoker was negative (n=374; OR=0.48, 95% CI: 0.28-0.81). Both underweight and overweight/obesity were positively associated with transition to regular smoking among women who did not report CSA (n=2076; OR=1.57, 95% CI: 1.05-2.35 and OR=1.73, 95% CI: 1.35-2.20, respectively). These results suggest that experiencing CSA alters the association between BMI and regular smoking in women who have experimented with cigarettes.
Smoking; body mass index; childhood sexual abuse; twins; MOAFTS
Variation in personality traits is 30% to 60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger’s temperament scales in a sample of 5117 individuals, in order to identify common genetic variants underlying variation in personality. Participants’ scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained.
genome-wide association; genes; personality; temperament; mutation; selection; maintenance of genetic variation; evolution
Peer substance involvement (PSI) is a robust correlate of adolescent substance use. A small number of genetically informative studies suggest that shared genetic and environmental factors contribute to this association but have not clarified our understanding of the mechanisms by which PSI influences the etiology of regular substance involvement (RSI), particularly in women.
We use data on 2,176 twin women, who were part of a population-based cohort from U.S. Midwest, to examine the relationship between self-reported PSI during adolescence and a composite regular substance involvement factor (RSI) representing regular tobacco, alcohol and cannabis use during young adulthood, using genetically informative correlation, moderation and joint correlation-moderation models.
There was evidence for a significant additive genetic X environment interaction. PSI was moderately heritable (h2=0.25). Genetic, shared and non-shared influences on RSI overlapped with influences on PSI, with common genetic factors accounting for 18.5% of the genetic influences on RSI. Even after controlling for these shared genetic influences, RSI was more heritable in those reporting greater PSI.
While young women may select peers based on certain dispositional traits (e.g. permissiveness towards substance use), the social milieu constructed by PSI does modify the architecture of increased RSI in those individuals with increasing levels of PSI being associated with stronger expression of heritable influences.
In adults, about 40% of the variance in risk of Major Depressive Disorder (MDD) is due to genetic factors, but little data exist on the heritability of youth MDD. The goal of this study was the genetic analysis of MDD in an epidemiologically and genetically representative sample of adolescent female twins.
A sample of 3416 female adolescent twins systematically ascertained from birth records was assessed using a structured telephone interview that included a comprehensive DSM-IV-based section for the diagnostic assessment of MDD. Mean subject age at time of assessment was 15.5 and participation rate exceeded 85%. Genetic modeling was conducted taking into consideration the problem of censoring, i.e., that younger adolescents were not through their period of risk for adolescent onset of MDD.
Lifetime self-reported MDD prevalence ranged from 1% under age 12 to 17.4% at age 19 and older. The genetic variance in risk of MDD was 40.4% (95% confidence interval (CI): 23.9–55.1), with the remaining variance explained by non-shared environmental effects 59.6% (95%CI: 44.9–76.1). Shared environmental effects were not significant. A significant recall bias was observed with older respondents on average reporting later onsets for their first episode of MDD.
The genetic and environmental contributions to risk of MDD in this representative sample of female adolescent twins are remarkably analogous to findings from adult samples. These results are congruent with a conceptualization of adolescent MDD and adult MDD as having very similar etiologic determinants.
Major Depressive Disorder; genetic epidemiology; adolescent twin studies
The aim of this study was to examine the association between initial subjective effects from cigarettes and the rate of progression from first cigarette to regular smoking. Latent class analysis (LCA) was applied to subjective effects data from 573 offspring of twins ranging in age from 14 to 32 years. LCA revealed four classes: 1) High on both pleasurable and physiological respondeses, 2) Cough only response, 3) High on physiological, low on pleasurable respondses, and 4) High on pleasurable, low on physiological respondses. Classes of responses were then used to predict time from first cigarette to the onset of regular smoking in a Cox proportional hazards model. Time-varying covariates representing relevant psychiatric and psychosocial factors as well as dummy variables representing the offspring-of-twins design were included in the model. Members of classes 1 and 4 transitioned more rapidly to regular smoking than the classes characterized as low on the pleasurable response dimension. Our findings provide evidence that previously reported associations between pleasurable initial experiences and progression to regular smoking hold true as well for the rate at which that transition occurs. Furthermore, the fact that profiles of responses did not fall into global categories of exclusively pleasurable vs. exclusively negative (physiological) responses suggests the importance of considering both dimensions in combination to characterize risk for smoking-related outcomes.
smoking; subjective effects; offspring of twins
Despite mounting evidence that use of and dependence on alcohol and cannabis are influenced by heritable factors, the extent to which heritable influences on these phenotypes overlap across the two substances has only rarely been explored. In the current study, we quantified cross-substance overlap in sources of variance and estimated the degree to which within-substance associations between use and dependence measures are attributable to common genetic and environmental factors for alcohol and cannabis.
The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 736 singletons) from the Australian Twin Registry, aged 24-36 years. Alcohol and cannabis use histories were collected via telephone diagnostic interviews and used to derive an alcohol consumption factor, a frequency measure for cannabis use, and DSM-IV alcohol and cannabis dependence symptom counts. Standard genetic analyses were conducted to produce a quadrivariate model that provided estimates of overlap in genetic and environmental influences across the four phenotypes.
Over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms, and just under 50% of variance in alcohol dependence (AD) symptoms were attributable to genetic sources. Shared environmental factors did not contribute significantly to the four phenotypes. Nearly complete overlap in heritable influences was observed for within-substance measures of use and dependence symptoms. Genetic correlations across substances were 0.68 and 0.62 for use and dependence symptoms, respectively.
Common heritable influences were evident for alcohol and cannabis use and for AD and cannabis dependence symptomatology, but findings indicate that substance-specific influences account for the majority of the genetic variance in the cannabis use and dependence phenotypes. By contrast, the substantial correlations between alcohol use and AD symptoms and between cannabis use and cannabis dependence symptoms suggest that measures of heaviness of use capture much of the same genetic liability for alcohol- and cannabis-related problems as dependence symptomatology.
alcohol dependence; cannabis dependence; genetics; twins
Previous research has reported a significant genetic correlation between heaviness of alcohol consumption and alcohol dependence (AD), but this association might be driven by the influence of AD on consumption rather than the reverse. We test the genetic overlap between AD symptoms and a heaviness of consumption measure among individuals who do not have AD. A high genetic correlation between these measures would suggest that a continuous measure of consumption may have a useful role in the discovery of genes contributing to dependence risk.
Factor analysis of 5 alcohol use measures was used to create a measure of heaviness of alcohol consumption. Quantitative genetic analyses of interview data from the 1989 Australian Twin Panel (n=6257 individuals; M=29.9 years) assessed the genetic overlap between heaviness of consumption, DSM-IV AD symptoms, DSM-IV AD symptom clustering, and DSM-IV alcohol abuse.
Genetic influences accounted for 30–51% of the variance in the alcohol measures and genetic correlations were 0.90 or higher for all measures, with the correlation between consumption and dependence symptoms among non-dependent individuals estimated at 0.97 (95% CI: 0.80–1.00).
Heaviness of consumption and AD symptoms have a high degree of genetic overlap even among non-dependent individuals in the general population, implying that genetic influences on dependence risk in the general population are acting to a considerable degree through heaviness of use, and that quantitative measures of consumption will likely have a useful role in the identification of genes contributing to AD.
alcohol dependence; heaviness of consumption; heritability; genetic overlap; twins; gene identification
The risks associated with early age at initiation for alcohol, cigarette, and cannabis use are well documented, yet the timing of first use has rarely been studied in genetically informative frameworks, leaving the relative contributions of genetic and environmental factors to age at initiation largely unknown. The current study assessed overlap in heritable and environmental influences on the timing of initiation across these three substances in African-American women, using a sample of 462 female twins (100 monozygotic and 131 dizygotic pairs) from the Missouri Adolescent Female Twin Study. Mean age at the time of interview was 25.1 years. Ages at first use of alcohol, cigarettes, and cannabis were gathered in diagnostic interviews administered over the telephone. Standard genetic analyses were conducted with substance use initiation variables categorized as never, late, and early onset. Variance in the timing of first use was attributable in large part to genetic sources: 44% for alcohol, 62% for cigarettes, and 77% for cannabis. Genetic correlations across substances ranged from 0.25 to 0.70. Shared environmental influences were modest for alcohol (10%) and absent for cigarettes and cannabis. Findings contrast with reports from earlier studies based on primarily Caucasian samples, which have suggested a substantial role for shared environment on substance use initiation when measured as lifetime use. By characterizing onset as timing of first use, we may be tapping a separate construct. Differences in findings may also reflect a distinct etiological pathway for substance use initiation in African-American women that could not be detected in previous studies.
Early initiation; Alcohol; Tobacco; Cannabis; Twins
Compared to those who reported a lifetime co-occurrence of cannabis and tobacco use, individuals who report simultaneous use of cannabis and tobacco are more likely to also report higher rates of substance-related problems and psychopathology. In a sample of young women, we examine (a) co-occurring use, or whether regular cigarette smoking is associated with increased cannabis involvement and (b) simultaneous use, a special form of co-occurring use where cannabis and cigarettes are typically used on the same occasion to test whether those who use cannabis and tobacco simultaneously are also more likely to report greater cannabis involvement and (c) the extent to which latent genetic and environmental factors contribute to simultaneous use in those with a history of co-occurring cannabis use and regular cigarette smoking. Women (N=3,427) who report regular cigarette smoking are 4.5–9.5 times more likely to report co-occurring cannabis use and other stages of cannabis involvement, including DSM-IV cannabis abuse and dependence. In those women who report co-occurring regular cigarette smoking and lifetime cannabis use (N=1,073), simultaneous use of cannabis and tobacco was associated with increased likelihood of negative cannabis-related outcomes. Simultaneous users were 1.6 times more likely to meet criteria for DSM-IV cannabis abuse, even after controlling for early covariates and for prior stages of cannabis involvement. Simultaneous use was not heritable, and twin similarity was attributable to shared environmental factors (31%). While our study does not determine causality between simultaneous tobacco-cannabis use and cannabis involvement, results indicate that simultaneous use is potentially a marker for more severe psychosocial consequences associated with cannabis use.
Simultaneous use; cannabis; tobacco; abuse; dependence; twin
To evaluate the possible association between maternal smoking during pregnancy (MSDP) and offspring outcomes of birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder (ADHD) and conduct problems (CD) while controlling for similar behaviors in parents.
Using telephone interviews, data were collected, in 2001 and 2004, as a part of two U.S. offspring-of-twins projects. Fathers, who were twins participating in the Vietnam Era Twin Registry, their female spouse and their offspring were interviewed – information on 1342 unique pregnancies in mothers with a history of regular smoking was utilized for these analyses. The association between MSDP and birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct disorder while controlling for similar behaviors in parents, was examined using regression.
MSDP was associated with decreased birth weight, low scholastic achievement, regular smoking and ADHD. However, the association between MSDP and offspring ADHD was explained by maternal ADHD. MSDP was also associated with earlier age of offspring initiation of smoking and onset of regular smoking.
MSDP may influence certain offspring outcomes via mechanisms that are independent from genetic risk attributable to comorbid conditions. Assisting expecting mothers with their smoking cessation efforts will likely provide widespread health benefits to both mother and offspring.
Childhood sexual abuse (CSA) and physical abuse (CPA) are well-established risk-factors for a wide of range of proximal and distal outcomes. The lack of availability of an optimal design for examining abuse and its consequences has resulted in the use of various approaches, each having its own limitations. We describe the Childhood Trauma Study which ascertained families from a large young adult Australian twin cohort on the basis of twins’ responses to screening questions assessing CSA and CPA. We report data from 3407 participants including twins, non-twin siblings, and their parents. Our data demonstrate the feasibility of using a comprehensive assessment to evaluate retrospective history of childhood abuse in an adult sample. We observed that risk for each form of abuse increased incrementally with the number of parents with alcohol problems. Psychometric properties of our measures of CSA and CPA including reasonable long-term stability, construct validity, and evidence of familial corroboration compare favorably with those of other reports in which samples were considerably younger and assessments were repeated over shorter intervals.
childhood sexual abuse; parental alcoholism; physical abuse; reliability; retrospective recall
Research suggests that individuals who start drinking at an early age are more likely to subsequently develop alcohol dependence. Twin studies have demonstrated that the liability to age at 1st drink and to alcohol dependence are influenced by common genetic and environmental factors, however, age at 1st drink may also environmentally mediate increased risk for alcohol dependence. In this study, we examine whether age at 1st drink moderates genetic and environmental influences, via gene x environment interactions, on DSM-IV alcohol dependence symptoms.
Using data on 6,257 adult monozygotic and dizygotic male and female twins from Australia, we examined the extent to which age at 1st drink (a) increased mean alcohol dependence symptoms and (b) whether the magnitude of additive genetic, shared and non-shared environmental influences on alcohol dependence symptoms varied as a function of increasing age at 1st drink. Twin models were fitted in Mx.
Risk for alcohol dependence symptoms increased with decreasing age at 1st drink. Heritable influences on alcohol dependence symptoms were considerably larger in those who reported an age at 1st drink prior to 13 years of age. In those with later onset of alcohol use, variance in alcohol dependence was largely attributable to non-shared environmental variance (and measurement error). This evidence for unmeasured gene x measured environment interaction persisted even when controlling for the genetic influences that overlapped between age at 1st drink and alcohol dependence symptoms.
Early age at 1st drink may facilitate the expression of genes associated with vulnerability to alcohol dependence symptoms. This is important to consider, not only from a public health standpoint, but also in future genomic studies of alcohol dependence.
To estimate the magnitude of genetic and environmental influences on timing of first alcohol use and alcohol dependence (AD) and to quantify the overlap in these influences across the two alcohol-related outcomes.
The sample consisted of 5,382 twins (2,691 complete pairs), aged 24 to 36 years, from the Australian Twin Registry.
History of alcohol use and DSM-IV alcohol dependence were assessed by structured telephone interview.
In both sexes, the relationship between age at first alcohol use and risk for AD followed a linear trend, such that the highest rates of AD were observed in individuals who began drinking at an earlier than average age (14 years or younger). Heritability estimates for timing of first alcohol use and AD were 36% and 53%, respectively. Shared environmental factors accounted for 15% of variance in initiation. There was no evidence of shared environmental influences on AD. The genetic correlation between timing of first alcohol use and AD was 0.59.
Findings highlight the substantial role of genetics in the development of AD and the early manifestation of that genetic risk in the timing of alcohol use initiation, which, unlike AD, is also influenced to a modest degree by shared environmental factors. The considerable overlap in heritable influences – and the virtual absence of overlap in individual-specific environmental influences – on initiation of alcohol use and AD indicates that the association between age at first drink and AD is attributable in large part to common genetic sources of variance.
initiation of alcohol use; alcohol dependence; twins