Gays, lesbians, and bisexuals (i.e. nonheterosexuals) have been found to be at much greater risk for many psychiatric symptoms and disorders, including depression. This may be due in part to prejudice and discrimination experienced by nonheterosexuals, but studies controlling for minority stress, or performed in very socially liberal countries, suggest that other mechanisms must also play a role. Here we test the viability of common cause (shared genetic or environmental etiology) explanations of elevated depression rates in nonheterosexuals.
A community-based sample of adult twins (N=9884 individuals) completed surveys investigating the genetics of psychiatric disorder, and were also asked about their sexual orientation. Large subsets of the sample were asked about adverse childhood experiences such as sexual abuse, physical abuse, and risky family environment, and also about number of older brothers, paternal and maternal age, and number of close friends. Data were analysed using the classical twin design.
Nonheterosexual males and females had higher rates of lifetime depression than their heterosexual counterparts. Genetic factors accounted for 31% and 44% of variation in sexual orientation and depression, respectively. Bivariate analysis revealed that genetic factors accounted for a majority (60%) of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were significant predictors of both sexual orientation and depression, further contributing to their correlation.
Nonheterosexual men and women had elevated rates of lifetime depression, partly due to shared etiological factors, although causality cannot be definitively resolved.
sexual orientation; childhood abuse; depression; twins; genetics
Understanding the relative contributions of genetic and environmental factors to trauma exposure, post-traumatic stress disorder (PTSD), and major depressive disorder (MDD) is critical to developing etiologic models of these conditions and their co-occurrence.
To quantify heritable influences on low-risk trauma, high-risk trauma, PTSD, and MDD and to estimate the degree of overlap between genetic and environmental sources of variance in these 4 phenotypes.
Adult twins and their siblings were ascertained from a large population-based sample of female and male twin pairs on the basis of screening items for childhood sexual abuse and physical abuse obtained in a previous assessment of this cohort.
Structured psychiatric telephone interviews.
Total sample size of 2591: 996 female and 536 male twins; 625 female and 434 male nontwin siblings.
Main Outcome Measure
Lifetime low- and high-risk trauma exposure, PTSD, and MDD.
In the best-fitting genetic model, 47% of the variance in low-risk trauma exposure and 60% of the variance in high-risk trauma exposure was attributable to additive genetic factors. Heritable influences accounted for 46% of the variance in PTSD and 27% of the variance in MDD. An extremely high degree of genetic overlap was observed between high-risk trauma exposure and both PTSD (r =0.89; 95% CI, 0.78-0.99) and MDD (r =0.89; 95% CI, 0.77-0.98). Complete correlation of genetic factors contributing to PTSD and to MDD (r=1.00) was observed.
The evidence suggests that almost all the heritable influences on high-risk trauma exposure, PTSD, and MDD, can be traced to the same sources; that is, genetic risk is not disorder specific. Individuals with a positive family history of either PTSD or MDD are at elevated risk for both disorders and should be closely monitored after a traumatic experience for symptoms of PTSD and MDD.
The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences. We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol-related problem, and first problem to onset of AD.
The sample consisted of 3,546 female twins from the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to 29 years. Retrospective reports of alcohol use histories were collected by telephone diagnostic interview and transition times between drinking milestones were coded ordinally. Standard genetic analyses were conducted in Mx to derive a trivariate model that provided estimates of genetic and environmental influences that were common as well as specific to the 3 transition times.
Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition-specific.
The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development. Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage-specific environmental contributions to alcohol outcomes in developing interventions.
Alcohol Dependence; Genetics; Women; Transition; Course
Early-onset alcohol use is associated with increased vulnerability to subsequent alcohol abuse and dependence. However, not all early-onset alcohol users develop alcohol use disorders (AUDs). Using a sample of young women from the U.S., we identify correlates that contribute to a greater likelihood of AUDs in early-onset alcohol users.
Using interview and questionnaire data on participants of the Missouri Adolescent Female Twin Study (MOAFTS), we examine whether measures from domains including socio-demographic, pubertal development, religiosity, educational achievement, adverse life events, internalizing disorders, externalizing disorders and family history and discipline were associated with development of AUDs in 1,158 women who had their first drink of alcohol prior to age 16.
Early-onset drinkers were 3.6 times more likely to meet criteria for AUDs than later onset drinkers. While univariate analyses revealed that a host of correlates were associated with likelihood of AUDs in early-onset drinkers, multivariate analyses suggested that, even after accounting for a particularly early age of onset of drinking, those with a history of physical abuse, co-twin alcohol problems, conduct disorder, regular smoking, older peers and peer substance use were considerably more likely to meet criteria for AUDs than early onset drinkers without a lifetime history of these correlates.
The progression from first drink to AUDs is complex, and while early age at first drink is a potent risk factor, other aspects of psychopathology, family history, conduct problems and peer affiliations can exacerbate or alleviate the risk of AUDs in these young female drinkers.
alcohol; early-onset; alcohol abuse/dependence; female
The Hangover Symptoms Scale (HSS) assesses the frequency of 13 symptoms experienced after drinking in the past year. Cross-sectional analyses in college drinkers showed preliminary evidence for the validity of the HSS (Slutske et al., 2003). The current investigation extended this work by examining the construct validity of the HSS in an ecological momentary assessment investigation.
Frequent drinkers (N = 404) carried electronic diaries to track their daily experiences over three weeks. Each morning, the diary assessed prior-night drinking behaviors, the presence of current hangover, and intensity of current headache and nausea.
Adjusting for sex and body mass, the HSS significantly predicted diary endorsement of hangover (OR = 2.11, 95% CI = 1.78–2.49, p <.001). Participants who endorsed the HSS headache and nausea items were especially likely to report elevations of corresponding symptoms in diary records made the morning after drinking. HSS scores incrementally predicted hangover when the number of drinks consumed in the episode was covaried but did not moderate the relationship between the number of drinks and diary hangover reports.
The HSS appears to be a valid tool for hangover research. Higher HSS scores identify individuals who complain of “real world” hangovers and who may be especially likely to display particular symptoms after a night of drinking. Past hangovers predicted future hangovers, suggesting hangovers do not necessarily discourage or inhibit future drinking, at least across the several-week time interval studied here. There is a need to develop and evaluate complementary measures that can more directly index individual differences in hangover susceptibility in survey designs.
hangover; symptoms; questionnaire; Hangover Symptoms Scale; ecological momentary assessment
Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ between human populations when viewed from the perspective of component microbial lineages, encoded metabolic functions, stage of postnatal development, and environmental exposures, we characterized bacterial species present in fecal samples obtained from 531 individuals representing healthy Amerindians from the Amazonas of Venezuela, residents of rural Malawian communities, and inhabitants of USA metropolitan areas, as well as the gene content of 110 of their microbiomes. This cohort encompassed infants, children, teenagers and adults, parents and offspring, and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the representation of genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial species assemblages and functional gene repertoires were noted between individuals residing in the USA compared to the other two countries. These distinctive features are evident in early infancy as well as adulthood. In addition, the similarity of fecal microbiomes among family members extends across cultures. These findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of Westernization.
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.
Genetic risk for alcohol dependence has been shown to overlap with genetic factors contributing to variation in dimensions of personality. Though drinking motives have been posited as important mediators of the alcohol-personality relation, the extent to which the genetic covariance between alcohol use disorder (AUD) symptoms (i.e. abuse and dependence criteria) and personality is explained by genetic factors contributing to variation in drinking motives remains unclear.
Using data from 2,904 young adult female twins, the phenotypic and genetic associations among personality dimensions (constraint [measured by the Multidimensional Personality Questionnaire; Tellegen, 1982], conscientiousness, neuroticism, and agreeableness [measured by the NEO-PI; Costa & McCrae, 1985]), internal drinking motives (enhancement and coping motives [measured by the Drinking Motive Questionnaire; Cooper, 1994]), and AUD symptoms were tested.
Significant genetic associations were found between all personality measures and AUD symptoms. Coping motives showed significant genetic overlap with AUD symptoms and most personality measures, whereas enhancement motives were not significantly heritable. Adjusting for coping motives, genetic correlations between AUD symptoms and traits of neuroticism and agreeableness were no longer statistically significant.
Findings suggest that genetic variation in drinking to cope might account for a considerable proportion of the genetic covariance between specific personality dimensions and AUD symptoms.
behavior genetics; personality; drinking motives; alcohol use disorders
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.
Many states require screening of individuals arrested for driving under the influence of alcohol (DUI) to determine recidivism risk and the need for treatment based on severity of alcohol problems. Several screening instruments use DSM-IV criteria for alcohol abuse and dependence to assess alcohol problems in this population, but whether they adequately measure alcohol problems in individuals with DUIs has not been examined. In addition, gender differences in DUI samples suggest that female offenders have more severe alcohol problems than male offenders. The current study examines differences in alcohol criteria functioning by DUI history and gender using an item response theory (IRT) approach.
Data from diagnostic interviews with 8605 participants in the Collaborative Study on the Genetics of Alcoholism, including 1655 who ever reported a DUI arrest (20% women), were used to examine differences in alcohol criteria functioning between men and women with and without DUIs. The factor underlying item response was conceptualized as unidimensional, representing alcohol problem severity.
Social/interpersonal problems, larger/longer, and inability/persistent desire to quit displayed greater discrimination of IRT-defined alcohol problem severity among individuals with DUIs than those without. Irrespective of DUI status, women had a higher threshold than men for time spent drinking or recovering. Women without DUIs had a higher threshold than similar men for social/interpersonal problems. Taken as a whole, the criteria yielded similar amounts of information in all groups.
DSM-IV criteria for alcohol abuse and dependence adequately detect alcohol problem severity in individuals with DUIs and some are better at detecting severity in this particularly high-risk group than in individuals without DUIs. However, the criteria as a whole are equally effective in measuring alcohol problem severity among individuals with and without DUIs, and may be used with confidence in screening DUI offenders.
DUI; Alcohol Use Disorder; Item Response Theory
To determine the prevalence of past 12 month DSM-5 alcohol use disorders (AUDs), to quantify and characterize individuals who remain stably unaffected or affected and those who diagnostically “switch” between DSM-IV and DSM-5 classifications.
Data from the nationally representative Wave 2 of the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) collected in 2004–2005.
General population survey.
All surveyed participants (N=34,653, aged 21 and older) and 29,993 individuals reporting lifetime alcohol use across both waves of NESARC.
DSM-IV and DSM-5 criteria were coded using proposed guidelines.
The prevalence of DSM-5 AUDs was 10.8% with the corresponding prevalence of DSM-IV abuse/dependence being 9.7%, implying a modest 11.3% increase. Those who diagnostically switched from affected to unaffected (19.6% of DSM-IV affected) were most likely to have endorsed hazardous use, particularly due to drinking and driving while those who transitioned from unaffected to affected (3.3% of DSM-IV unaffected) were primarily DSM-IV diagnostic orphans reporting larger/longer and quit/cut-back. Dropping the legal criterion did not significantly affect the prevalence while the addition of craving also had a relatively modest impact on prevalence.
The proposed DSM-5 revisions successfully eliminate individuals previously diagnosed with DSM-IV alcohol abuse primarily due to hazardous use alone and incorporate diagnostic orphans into the diagnostic realm. Definitions of craving and importantly, hazardous use require considerable attention as it is likely that they will contribute to variations in reports of increased prevalence of AUDs between DSM-IV to DSM-5.
alcohol; Alcohol Use Disorders; DSM-5; NESARC
Human mate choice is central to individuals’ lives and to the evolution of the species, but the basis of variation in mate choice is not well understood. Here we look at a large community-based sample of twins and their partners and parents (N > 20,000 individuals) to test for genetic and family environmental influences on mate choice, with and without controlling for the effects of assortative mating. Key traits are analyzed, including height, body mass index, age, education, income, personality, social attitudes, and religiosity. This revealed near-zero genetic influences on male and female mate choice over all traits and no significant genetic influences on mate choice for any specific trait. A significant family environmental influence was found for the age and income of females’ mate choices, possibly reflecting parental influence over mating decisions. We also tested for evidence of sexual imprinting, where individuals acquire mate-choice criteria during development by using their opposite-sex parent as the template of a desirable mate; there was no such effect for any trait. The main discernable pattern to mate choice was assortative mating; we found that partner similarity was due to initial choice rather than convergence and also due at least in part to phenotypic matching.
mate choice; mate preferences; behaviour genetics; evolutionary psychology; sexual imprinting; assortative mating
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 moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50–60% heritability), with high correlation of genetic influences, we have conducted a quantitative trait genomewide association study for phenotypes related to alcohol use and dependence.
Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genomewide SNP genotyping was performed with 8754 individuals [2062 alcohol dependent cases] selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genomewide SNP data.
No findings reached genomewide significance (p=8.4×10−8 for this study), with lowest p-value for primary phenotypes of 1.2×10−7. Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk.
We conclude that (i) meta-analyses of consumption data may contribute usefully to gene-discovery; (ii) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; (iii) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g. prospective high-risk or resilience studies).
Alcoholism; genome-wide association; quantitative-trait; non-replication
Motivational models of alcohol use propose that the motivation to consume alcohol is the final common pathway to its use. Both alcohol consumption and drinking motives are influenced by latent genetic factors that partially overlap. This study investigated whether drinking motives mediate the associations between alcohol consumption and 2 single-nucleotide polymorphisms (SNPs) from genes involved in serotonin (TPH2; rs1386496) and dopamine synthesis (DDC; rs3779084). Based on earlier work showing that enhancement and coping motives were heritable in regular smokers but not in nonregular smokers, we hypothesized these motives would mediate the relationships between alcohol consumption and these SNPs in regular smokers.
Drinking motives data were available from 830 young adult female twins (n = 344 regular smokers and n = 486 never/nonregular smokers). We used confirmatory factor analyses to model enhancement, coping, and alcohol consumption factors and to conduct mediation analyses in the regular smoker and never/nonregular smoker groups.
Our hypothesis was partially supported. The relationship between alcohol consumption and rs1386496 was not mediated by drinking motives in either group. However, in the regular smokers, the relationship between alcohol consumption and rs3779084 was mediated by enhancement and coping motives. Carriers of the rs3779084 minor allele who were regular smokers reported more motivation to consume alcohol. Given this pattern of results was absent in the never/nonregular smokers, our results are consistent with a gene × smoking status interaction.
In regular smokers, variability at the locus marked by rs3779084 in the DDC gene appears to index biologically based individual differences in the motivation to consume alcohol to attain or improve a positive affective state or to relieve a negative one. These results could be because of increased sensitivity to the reinforcing effects of alcohol among minor allele carriers who smoke, which might be due to structural or functional differences in mesorticolimic dopamine “reward” circuitry.
Alcohol; Tobacco; Drinking Motives; DDC; TPH2; Mediation
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 manifestation of alcohol dependence at different developmental stages may be associated with different genetic and environmental factors. Taking a developmental approach, the current study characterized interaction between the dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism and developmentally specific environmental factors (childhood adversity, college/Greek involvement, and delayed adult role transition) on alcohol dependence during emerging and young adulthood. Prospective data were obtained from a cohort of 234 Caucasian individuals (56% female) followed up at ages 18 through 34. A longitudinal hierarchical factor model was estimated to model a trait-like persistent alcohol dependence factor throughout emerging and young adulthood and two residual state-like alcohol dependence factors limited to emerging adulthood and young adulthood, respectively. To account for those alcohol dependence factors, three two-way interaction effects between the DRD4 VNTR polymorphism and the three developmentally specific environment factors were modeled. Carriers of the DRD4 long allele showed greater susceptibility to environmental effects; they showed more persistent alcohol dependence symptoms as childhood adversity increased and more alcohol dependence symptoms limited to emerging adulthood as college/Greek involvement increased. Alcohol dependence among non-carriers of the long allele, however, did not differ as a function of those environments. Although replication is necessary, these findings highlight the importance of repeated phenotypic assessments across development and modeling both distal and proximal environments and their interaction with genetic susceptibility at specific developmental stages.
DRD4 VNTR; alcohol; gene-environment interaction; development
A genetic factor model is introduced for decomposition of group differences of the means of phenotypic behavior as well as individual differences when the research variables under consideration are ordered categorical. The model employs the general Genetic Factor Model proposed by Neale and Cardon (Methodology for genetic studies of twins and families, 1992) and, more specifically, the extension proposed by Dolan et al. (Behav Genet 22: 319–335, 1992) which enables decomposition of group differences of the means associated with genetic and environmental factors. Using a Latent Response Variable (LRV) formulation (Muthén and Asparouhov, Latent variable analysis with categorical outcomes: multiple-group and growth modeling in Mplus. Mplus web notes: No. 4, Version 5, 2002), proportional differences of response categories between groups are modeled within the genetic factor model in terms of the distributional differences of latent response variables assumed to underlie the observed ordered categorical variables. Use of the proposed model is illustrated using a measure of conservatism in the data collected from the Australian Twin Registry.
genetic factor model; latent response variable formulation; ordered categorical variables; Mplus; twins
Outcome expectancy is a central construct in models of addiction. Several outcome expectancies associated with smoking cigarettes have been identified, and studies suggest that individual differences in smoking expectancies are related to important aspects of tobacco use, including levels of smoking, nicotine dependence and smoking cessation. In the present study, we used a novel analytic method, exploratory structural equation modeling (ESEM), to quantify smoking expectancies from a subset of items adapted from the Smoking Consequences Questionnaire (SCQ; Brandon and Baker, 1991) and SCQ-Adult (Copeland et al., 1995). In our sample of 1262 monozygotic and dizygotic young adult, female twins who were regular smokers, we quantified six smoking expectancy factors similar to those reported in previous studies. These included Negative Affect Reduction, Boredom Reduction, Weight Control, Taste Manipulation, Craving/Addiction and Stimulation-State Enhancement. We used genetic model-fitting to examine the extent to which individual differences in the expectancies were influenced by latent genetic, shared environmental and non-shared environmental factors. We also examined the validity of the expectancy factors by examining their associations with nicotine dependence (ND) before and after adjusting for comorbid diagnoses of drug dependence and alcohol use disorder. Results of the validity analysis indicated that all of the expectancies were associated with ND after covariate adjustment. Although we lacked the statistical power to distinguish between genetic and shared environmental sources of variance, our results suggest that smoking outcome expectancies aggregate in families, but the majority of variance in these expectancies is due to environmental factors specific to the individual.
Smoking expectancies; Smoking Consequences Questionnaire; Nicotine Dependence; Genetics; Female
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
Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled median or mean test statistic for association calculated from multiple single-nucleotide-polymorphisms across the genome is used to assess such effects, and ‘genomic control' can be applied subsequently to adjust test statistics at individual loci by a genomic inflation factor. Published GWAS have clearly shown that there are many loci underlying genetic variation for a wide range of complex diseases and traits, implying that a substantial proportion of the genome should show inflation of the test statistic. Here, we show by theory, simulation and analysis of data that in the absence of population structure and other technical artefacts, but in the presence of polygenic inheritance, substantial genomic inflation is expected. Its magnitude depends on sample size, heritability, linkage disequilibrium structure and the number of causal variants. Our predictions are consistent with empirical observations on height in independent samples of ∼4000 and ∼133 000 individuals.
genome-wide association study; genomic inflation factor; polygenic inheritance
Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior were examined in a large community sample of 6,383 adult male, female, and opposite-sex twins. Retrospective reports of childhood conduct disorder (prior to age 18) were obtained when participants were approximately 30 years old, and lifetime reports of adult antisocial behavior (antisocial behavior after age 17) were obtained eight years later. Results revealed that either the genetic or shared environmental factors influencing childhood conduct disorder differed for males and females (i.e., a qualitative sex difference), but by adulthood, these sex-specific influences on antisocial behavior were no longer apparent. Further, genetic and environmental influences accounted for proportionally the same amount of variance in antisocial behavior for males and females in childhood and adulthood (i.e., no quantitative sex differences). Additionally, the stability of antisocial behavior from childhood to adulthood was slightly greater for males than females. Though familial factors accounted for more of the stability of antisocial behavior for males than females, genetic factors accounted for the majority of the covariation between childhood conduct disorder and adult antisocial behavior for both sexes. The genetic influences on adult antisocial behavior overlapped completely with the genetic influences on childhood conduct disorder for both males and females. Implications for future twin and molecular genetic studies are discussed.
A recent meta-analysis of genome-wide association (GWA) studies identified 95 loci that influence lipid traits in the adult population and found that collectively these explained about 25–30% of heritability for each trait. Little is known about how these loci affect lipid levels in early life, but there is evidence that genetic effects on HDL- and LDL-cholesterol (HDL-C, LDL-C) and triglycerides vary with age. We studied Australian adults (N = 10,151) and adolescents (N = 2,363) who participated in twin and family studies and for whom we have lipid phenotypes and genotype information for 91 of the 95 genetic variants. Heterogeneity tests between effect sizes in adult and adolescent cohorts showed an excess of heterogeneity for HDL-C (pHet<0.05 at 5 out of 37 loci), but no more than expected by chance for LDL-C (1 out of 14 loci), or trigycerides (0 out 24). There were 2 (out of 5) with opposite direction of effect in adolescents compared to adults for HDL-C, but none for LDL-C. The biggest difference in effect size was for LDL-C at rs6511720 near LDLR, adolescents (0.021±0.033 mmol/L) and adults (0.157±0.023 mmol/L), pHet = 0.013; followed by ZNF664 (pHet = 0.018) and PABPC4 (pHet = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults.