Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder.

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Childhood Trauma and Two Stages of Alcohol Use in African American and European American Women: Findings from a Female Twin Sample.

The current investigation assessed for moderating effects of childhood trauma on genetic and environmental contributions to timing of alcohol use initiation and alcohol use disorder in African American (AA) and European American (EA) women. Data were drawn from diagnostic telephone interviews conducted with 3786 participants (14.6% AA) in a longitudinal female twin study. Childhood trauma was defined alternately as child maltreatment and more broadly to include other events (e.g., witnessing violence). Phenotypic associations between childhood trauma and alcohol outcomes were estimated using logistic regression analyses. Twin modeling was conducted to test for moderating effects of childhood trauma on the contributions of genetic and environmental factors to timing of initiation and alcohol use disorder. Under both definitions, childhood trauma was associated with early initiation (relative risk ratios: 1.90, 1.72) and alcohol use disorder (odds ratios: 1.92, 1.76). Yet gene by environment effects were observed only for child maltreatment and timing of initiation in EA women, with heritable influences less prominent in those who had experienced child maltreatment (0.35, 95% CI: 0.05-0.66 vs. 0.52, 95% CI: 0.30-0.73). We found more similarities than differences in the association of childhood trauma with alcohol outcomes across racial/ethnic groups, trauma type, and stages of alcohol use. However, findings suggest that the relative contribution of genetic factors to alcohol outcomes differs by childhood maltreatment history in EA women specifically in the earliest stage of alcohol use.

Differences between White and Black young women in the relationship between religious service attendance and alcohol involvement.

BACKGROUND AND OBJECTIVES: We examined the associations of religious attendance during childhood (C-RA) and adulthood (A-RA) with alcohol involvement (ever drinking, timing of first alcohol use, and alcohol use disorder [AUD]) in White and Black female twins. As genetic and environmental factors influence religious attendance and alcohol involvement, we examined the extent to which they contribute to their association. METHODS: Data on 3,234 White and 553 Black female twins (18-29 years) from the Missouri Adolescent Female twin Study. Significant correlations between C-RA or A-RA and alcohol involvement were parsed into their additive genetic, shared environmental, and individual-specific environmental sources. RESULTS: C-RA was associated with ever drinking and timing of first alcohol use in Whites. A-RA was associated with ever drinking and AUD in both Whites and Blacks. Shared environmental influences did not contribute to alcohol or religiosity phenotypes in Blacks. In Whites, the association between C-RA and alcohol was due to shared environmental influences, whereas the association between A-RA and alcohol was attributable to additive genetic, shared environmental, and individual-specific environmental sources. Individual-specific environment and genetics contributed to associations between A-RA and ever drinking and AUD, respectively, in Blacks. CONCLUSIONS: Factors other than C-RA contribute to lower rates of alcohol involvement in Blacks. Shared environment does not contribute to links between A-RA and alcohol involvement in Blacks. SCIENTIFIC SIGNIFICANCE: The protective impact of childhood religiosity on alcohol use and misuse is important in Whites and is due to familial factors shared by religiosity and alcohol involvement. (Am J Addict 2017;26:437-445).

Progression from First Drink, First Intoxication, and Regular Drinking to Alcohol Use Disorder: A Comparison of African American and European American Youth.

BACKGROUND: Differences between African Americans (AAs) and European Americans (EAs) in the prevalence and age at onset of alcohol use and alcohol use disorder (AUD) have been documented, but distinctions in the timing of early stage transitions and contribution of various psychiatric and psychosocial risk factors to the progression from initiation to AUD have yet to be investigated. The current study characterized progression from alcohol use initiation-defined alternatively as first drink, first intoxication, and regular drinking onset-to AUD in AA and EA youth. METHODS: Psychiatric interviews were administered via telephone to 1,461 participants (56% AA, 44% EA) in a high-risk family study (50.3% female, mean age = 17.6 [SD = 3.8]). Cox proportional hazards regression analyses were conducted separately for the AA and EA subsamples to predict DSM-5 AUD as a function of age at alcohol use initiation, with age at first drink, age at first intoxication, and age at regular drinking onset as the point of origin in separate models. RESULTS: Across race/ethnicity, regardless of how it was measured, early alcohol use initiation predicted AUD, but hazard ratios (HRs) were lowest for first drink. Regular smoking and social anxiety disorder were significant predictors in both racial/ethnic groups, but associations with conduct disorder (all 3 models: HR range = 2.07 to 4.15) and major depressive disorder (regular drinking: HR = 4.51, confidence interval [CI]: 1.60 to 12.69 for AUD onset ≥ age 20) were specific to AAs. Posttraumatic stress disorder (HR = 5.38, CI: 1.44 to 20.08) and generalized anxiety disorder (HR = 7.35, CI: 2.31 to 23.34 for AUD onset ≤ age 17) were strongly associated with progression from regular drinking to AUD exclusively in EAs. CONCLUSIONS: Early alcohol use initiation is a marker of risk for AUD in both AA and EA youth, but the contributions of various psychiatric risk factors to the development of AUD are not universal across racial/ethnic groups.

Association of Specific Traumatic Experiences With Alcohol Initiation and Transitions to Problem Use in European American and African American Women.

BACKGROUND: The aims of this study were to (i) characterize racial differences in alcohol involvement and (ii) examine the risk conferred by specific trauma exposures and posttraumatic stress disorder (PTSD) for different stages of alcohol involvement in European American (EA) and African American (AA) women. METHODS: Data are from the Missouri Adolescent Female Twins Study (N = 3,787, 14.6% AA; mean age at most recent interview = 24.5 [SD 2.8]). Trauma exposures (e.g., sexual abuse [SA], physical abuse [PA], witnessing another person being killed or injured, experiencing an accident, and experiencing a disaster) were modeled as time-varying predictors of alcohol initiation, transition to first alcohol use disorder (AUD) symptom, and transition to AUD diagnosis using Cox proportional hazards regression while taking into account other substance involvement, parental characteristics, and commonly co-occurring psychiatric disorders. RESULTS: In EA women only, SA was associated with alcohol initiation prior to the age of 14, PA predicted transition from initiation to first AUD symptom, and PA, witnessing injury or death, and SA predicted transition to AUD diagnosis. No association was discovered between trauma exposures or PTSD for any stage of alcohol involvement in AA women. CONCLUSIONS: Results reveal trauma experiences as important contributors to all stages of alcohol involvement in EA women only, with different trauma types conferring risk for each stage of alcohol involvement. PTSD was not revealed as a significant predictor of AUD in EA or AA women, suggesting trauma, independent of PTSD, directly contributes to alcohol involvement. Findings highlight the importance of considering racial differences when developing etiologic models of the association of traumatic experiences with alcohol involvement.

Familial influences on the full range of variability in attention and activity levels during adolescence: A longitudinal twin study.

To investigate familial influences on the full range of variability in attention and activity across adolescence, we collected maternal ratings of 339 twin pairs at ages 12, 14, and 16, and estimated the transmitted and new familial influences on attention and activity as measured by the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale. Familial influences were substantial for both traits across adolescence: genetic influences accounted for 54%-73% (attention) and 31%-73% (activity) of the total variance, and shared environmental influences accounted for 0%-22% of the attention variance and 13%-57% of the activity variance. The longitudinal stability of individual differences in attention and activity was largely accounted for by familial influences transmitted from previous ages. Innovations over adolescence were also partially attributable to familial influences. Studying the full range of variability in attention and activity may facilitate our understanding of attention-deficit/hyperactivity disorder's etiology and intervention.

Bulimic Behaviors and Early Substance Use: Findings from a Cotwin-Control Study.

BACKGROUND: Bulimic behaviors (i.e., binge eating and compensatory behaviors) and substance use frequently co-occur. However, the etiology underlying this association is poorly understood. This study evaluated the association between bulimic behaviors and early substance use, controlling for genetic and shared environmental factors. METHODS: Participants were 3,540 young adult women from the Missouri Adolescent Female Twin Study. A telephone adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism interview assessed DSM-IV bulimic behaviors, substance use, and other psychological characteristics. Lifetime bulimic behaviors were examined in twin pairs concordant and discordant for early substance use. Logistic regressions were adjusted for the nonindependence of twin data, zygosity, age, body mass index, early menarche (onset before age 12), and early sex (first consensual sexual intercourse before age 15). RESULTS: In the entire study population, women who reported early use of alcohol or nicotine were more likely to engage in bulimic behaviors after adjusting for covariates. In 53 pairs of monozygotic twins discordant for alcohol experimentation before age 15, the twin who reported early alcohol experimentation had 3.21 (95% confidence interval = 1.54 to 6.67) times higher odds of reporting bulimic behaviors than the cotwin who did not report early alcohol experimentation, even after adjustment for covariates. CONCLUSIONS: Findings suggest that early alcohol experimentation may contribute to the development of bulimic behaviors via mechanisms extending beyond shared vulnerability, including individual-specific environmental experiences or causal pathways.

Parental Separation and Offspring Alcohol Involvement: Findings from Offspring of Alcoholic and Drug Dependent Twin Fathers.

BACKGROUND: We examined associations between parental separation during childhood and offspring alcohol involvement, adjusting for genetic and environmental risks specific to parental alcohol (AD) and cannabis/other illicit drug dependence (DD). METHODS: The sample consisted of 1,828 offspring of male twins from the Vietnam Era Twin (VET) Registry, who completed a telephone diagnostic interview. Cox proportional hazards regression analyses were conducted predicting onset of first use, transition from first use to first AD symptom, and transition from first use to AD diagnosis from paternal and avuncular AD and DD history, parental separation, and offspring and family background characteristics. Paternal/avuncular DD/AD was based on the DSM-III-R; offspring and maternal AD were based on DSM-IV criteria. RESULTS: Paternal DD/AD predicted increased offspring risk for all transitions, with genetic effects suggested on rate of transitioning to AD diagnosis. Parental separation was predictive of increased risk for early alcohol use, but a reduced rate of transition to both AD symptom onset and onset of AD. No interactions between separation and familial risk (indexed by paternal or avuncular DD/AD) were found. CONCLUSIONS: Findings highlight the contribution of both parental separation and paternal substance dependence in predicting timing of offspring alcohol initiation and problems across adolescence into early adulthood.

Early onset alcohol use and self-harm: a discordant twin analysis.

BACKGROUND: Self-harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Although early onset alcohol use (EAU) has been causally linked to maladaptive clinical outcomes, its association with self-harm is less well characterized. This study aimed to further examine the link between EAU and both nonsuicidal self-injury (NSSI) and suicide attempt (SA), and elucidate shared familial and causal/individual-specific pathways that explain this co-occurrence. METHODS: Using data from 6,082 Australian same-sex twin pairs (1,732 monozygotic [MZ] and 1,309 dizygotic [DZ]), ages 23 to 40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio (OR) of self-harm within twin pairs discordant for EAU. RESULTS: Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly 4-fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across MZ and DZ twins. EAU also was associated with elevated odds of NSSI (OR = 7.62), although this was only the case for DZ twins in discordant pairs. CONCLUSIONS: The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual-specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI.

Prevalence of and familial influences on purging disorder in a community sample of female twins.

OBJECTIVE: Purging disorder (PD) was recently included as an otherwise specified feeding or eating disorder (OSFED) in the DSM-5; however, limited information is available on its prevalence, and its etiology is unknown. METHOD: Data from 1,790 monozygotic and 1,440 dizygotic European American female twins (age range = 18-29 years) from the Missouri Adolescent Female Twin Study were used to investigate prevalence and familial influences for PD. A structured clinical interview assessed lifetime DSM-IV criteria for eating disorders and PD. After adjustment for age, twin correlations and biometrical twin models were used to estimate familial (i.e., genetic plus shared environmental) influences on PD. RESULTS: One hundred and twenty one (3.77%; 95% CI: 3.14, 4.49) women met criteria for lifetime PD. Twin correlations suggested that genetic, shared environmental, and nonshared environmental factors influenced liability to PD. Nonshared environmental factors accounted for 56% [35%, 79%] of the variance in PD. Although familial effects accounted for a significant proportion of variance (44% [21%, 65%]), it was not possible to disentangle the independent contributions of additive genetic effects (20% [0%, 65%]) and shared environmental effects (24% [0%, 57%]). DISCUSSION: PD is a prevalent form of eating pathology. Familial factors are relevant to the development of PD but do not demonstrate the magnitude of heritable factors found for other eating disorders.

Are there common familial influences for major depressive disorder and an overeating-binge eating dimension in both European American and African American female twins?

OBJECTIVE: Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups. METHOD: Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age. RESULTS: The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re = .26 [.09, .42]). DISCUSSION: Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups.

Genetic and environmental risk for major depression in African-American and European-American women.

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29-78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.

Refining the notion of maturing out: results from the national epidemiologic survey on alcohol and related conditions.

OBJECTIVES: Our aim was to determine if the decrease in drug use disorders with age is attributable to changes in persistence, as implied by the notion of maturing out. Also, we examined the association between role transitions and persistence, recurrence, and new onset of drug use disorders. METHODS: We performed secondary analysis of the 2 waves of the National Epidemiologic Survey on Alcohol and Related Conditions data (baseline assessment 2001-2002, follow-up conducted 2004-2005). We conducted logistic regressions and multinomial logistic regression to determine the effect of age on wave 2 diagnosis status, as well as the interaction between age and role transitions. RESULTS: Rates of persistence were stable over the life span, whereas rates of new onset and recurrence decreased with age. Changes in parenthood, marital, and employment status were associated with persistence, new onset, and recurrence. We found an interaction between marital status and age. CONCLUSIONS: Our findings challenge commonly held notions that the age-related decrease in drug use disorders is attributable to an increase in persistence, and that the effects of role transitions are stronger during young, compared with middle and older, adulthood.

Associations of alcohol, nicotine, cannabis, and drug use/dependence with educational attainment: evidence from cotwin-control analyses.

BACKGROUND: Although substance use is associated with reduced educational attainment, this association may be owing to common risk factors such as socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug use and dependence were associated with lifetime educational attainment after controlling for familial background characteristics. METHODS: Data were from a 1987 questionnaire and a 1992 telephone diagnostic interview of 6,242 male twins (n = 3,121 pairs; mean age = 41.9 years in 1992) who served in the U.S. military during the Vietnam era and therefore, were eligible for educational benefits after military service. Reduced educational attainment (<16 years) was examined in twin pairs discordant for substance use history. Substance use and dependence risk factors assessed were early alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence. RESULTS: Three significant differences were observed between at-risk twins and their cotwins: Compared to their low-risk cotwins, likelihood of completing <16 years of education was significantly increased for the following: (i) twins who used alcohol before age 18 (adjusted OR = 1.44; 95% CI: 1.02 to 2.05), (ii) twins with a lifetime alcohol dependence diagnosis (adjusted OR = 1.76; 95% CI: 1.27 to 2.44), and (iii) twins who had used nicotine daily for 30 or more days (adjusted OR = 2.54, 95% CI: 1.55 to 4.17). However, no differences in education were observed among twin pairs discordant for cannabis initiation, early cannabis use, or cannabis, nicotine, or any illicit drug dependence. CONCLUSIONS: Even in a veteran population with access to military educational benefits, early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with years of education after controlling for shared familial contributions to educational attainment. The association between other substances and educational attainment was explained by familial factors common to these substance use phenotypes and adult educational attainment.

The interpretability of family history reports of alcoholism in general community samples: findings in a midwestern U.S. twin birth cohort.

BACKGROUND: Although there is a long tradition in alcoholism research of using family history ratings, the interpretability of family history reports of alcoholism from general community samples has yet to be established. METHODS: Telephone interview data obtained from a large cohort of female like-sex twins (N = 3,787, median age 22) and their biological parents (N = 2,928, assessed at twins' median age 15) were analyzed to determine agreement between parent self-report, parent ratings of coparent, and twin narrow (alcohol problems) and broad (problem or excessive drinking) ratings of each parent. RESULTS: In European ancestry (EA) families, high tetrachoric correlations were observed between twin and cotwin ratings of parental alcohol problems, between twin and parent ratings of coparent alcohol problems using symptom-based and single-item assessments, as well as moderately high correlations between twin and both mother and father self-reports. In African American (AA) families, inter-rater agreement was substantially lower than for EA families, with no cases where father ratings of maternal alcohol problems agreed with either twin ratings or mother self-report, and both cotwin agreement and mother-twin agreement were reduced. Differences between EA and AA families were not explained by differences in years of cohabitation with father or mother's education; however, underreporting of problems by AA parents may have contributed. CONCLUSIONS: Results support the use of family history ratings of parental alcoholism in general community surveys for EA families, but suggest that family history assessment in AA families requires improved methods.

Suicidal behavior, smoking, and familial vulnerability.

INTRODUCTION: Smoking is a well-established correlate of suicidal behavior. It is not known if familial risk factors contribute to this association. METHODS: Data were obtained via semistructured interviews with 1,107 twin fathers, 1,919 offspring between ages 12-32 years, and 1,023 mothers. Familial vulnerability to nicotine dependence and suicidal behavior was modeled via father and maternal self-report of these behaviors. Multinomial logistic regression models were computed with and without familial risk factors to estimate the association between offspring ever smoking, regular smoking, nicotine dependence, and a 4-level offspring suicide variable: (a) none, (b) ideation, (c) ideation + plan, and (d) ideation + plan + attempt or ideation + attempt. All models were stratified by gender and adjusted for sociodemographics, familial risk factors including parental suicidal behavior, nicotine dependence, and conduct disorder, and offspring conduct disorder, depression, alcohol abuse/dependence, and illicit drug abuse/dependence. RESULTS: After adjusting for covariates and familial risk factors, ever smoking was not significantly associated with suicidal behavior in males and females. In males, regular smoking was associated with ideation + plan (odds ratio [OR] = 5.47; 95% CI: 1.05-28.60), and in females, regular smoking was associated with ideation + plan + attempt or ideation + attempt. In both genders, nicotine-dependent smoking was associated with ideation + plan + attempt or ideation + attempt (males: OR = 6.59; 95% CI: 1.91-22.70, females: OR = 3.37; 95% CI: 1.25-9.04). Comparison of models with and without familial risk factors indicated that there is no mediation of smoking status and suicidal behavior by familial risk. CONCLUSIONS: Smoking and nicotine dependence are correlated with suicidal behaviour. Contributions from familial risk factors did not significantly alter this association.

Heritability of delay discounting in adolescence: a longitudinal twin study.

Delay discounting (DD) refers to the preference for smaller immediate rewards over larger but delayed rewards, and is considered to be a distinct component of a broader "impulsivity" construct. Although greater propensity for discounting the value of delayed gratification has been associated with a range of problem behaviors and substance abuse, particularly in adolescents, the origins of individual differences in DD remain unclear. We examined genetic and environmental influences on a real-life behavioral measure of DD using a longitudinal twin design. Adolescent participants were asked to choose between a smaller ($7) reward available immediately and a larger ($10) reward to be received in 7 days. Biometrical genetic analysis using linear structural equation modeling showed significant heritability of DD at ages 12 and 14 (30 and 51%, respectively) and suggested that the same genetic factors influenced the trait at both ages. DD was significantly associated with symptoms of conduct disorder, attention deficit hyperactivity disorder, substance use, and with higher novelty seeking and poor self-regulation. This study provides the first evidence for heritability of DD in humans and suggests that DD can be a promising endophenotype for genetic studies of addiction and externalizing disorders.

A candidate gene association study of alcohol consumption in young women.

BACKGROUND: 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 1,014 single-nucleotide polymorphisms in genes related to addiction. METHODS: 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 1,014 single-nucleotide polymorphisms (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. RESULTS: The top signals included clusters of SNPs in tryptophan hydroxylase 2 (TPH2) (e.g., rs1386496, p = 0.0003) and dopa decarboxylase (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 false discovery rate for the top signal (p = 0.0003) was 0.15, suggesting nominal significance only. Replication was limited and noted for 2 SNPs in ADH1C. CONCLUSIONS: 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.

A latent class analysis of DSM-IV and Fagerström (FTND) criteria for nicotine dependence.

BACKGROUND: Nicotine dependence is associated with considerable morbidity and mortality. Two predominant classification systems, the Diagnostic and Statistical Manual (DSM-IV) and Fagerström Test for Nicotine Dependence (FTND), have been used to measure liability to nicotine dependence, yet few studies have attempted to simultaneously examine both sets of criteria. METHODS: Using a sample of 624 regular smoking individuals who are offspring of Vietnam Era Twin fathers ascertained for an offspring of twin study, we applied latent class analysis to the 7 DSM-IV and the 6 FTND criteria to classify individuals by their nicotine dependence symptom profiles. Post-hoc across-class comparisons were conducted using a variety of smoking-related variables and aspects of psychopathology. Whether a single class identified offspring at high genetic and environmental vulnerability was also investigated. RESULTS: The cross-diagnosis kappa was .30. A 4-class solution fit these data best. The classes included a low DSM-low FTND class and a high DSM-high FTND class; a moderate DSM-moderate FTND class, which was distinguished by moderate levels of smoking and intermediate levels of comorbid psychopathology; and a light smoking-moderate FTND class consisting primarily of lighter smokers with a more recent onset of regular smoking. High genetic and environmental vulnerability to nicotine dependence was noted in all classes with no statistically significant across-class differences. CONCLUSIONS: In general, the DSM-IV and FTND criteria performed similarly to define a continuum of risk for nicotine dependence. The emerging class of light smokers should be further investigated to assess whether they transition to another class or remain as such.

Common genetic contributions to alcohol and cannabis use and dependence symptomatology.

BACKGROUND: 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 2 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. METHODS: The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 735 singletons) from the Australian Twin Registry, aged 24 to 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 4 phenotypes. RESULTS: 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 4 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. CONCLUSIONS: 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 to alcohol- and cannabis-related problems as dependence symptomatology.