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1.
Addiction ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351443

RESUMO

AIMS: To assess whether having multiple convictions for driving while under the influence of alcohol (MDUI) in women is a risk factor for maternal, infant and child mortality. DESIGN: Retrospective cohort design using record linkage, comparing women with MDUI convictions with propensity-matched women without alcohol-related driving offences ascertained through state records, on rates of maternal, infant and child mortality. SETTING: Missouri, United States. PARTICIPANTS: MDUI women (n = 1658) and women with no alcohol-related driving convictions (control, n = 184 252) who gave birth from 2000 to 2004. MEASUREMENTS: Data were obtained from state administrative records and US Census data. The outcomes were maternal, infant and child mortality. The input variable was presence or absence of MDUI convictions. Propensity-matching variables were maternal (smoking during pregnancy, delayed prenatal care, previous child deaths, age at birth, mother Missouri-born, education, pre-pregnancy obesity, marital status), reproductive partner (un-named partner, race/ethnicity, education, DUI status) and census tract (socio-economic advantage, urbanicity) characteristics. FINDINGS: Women with MDUI convictions had higher odds of maternal, infant and child mortality than propensity-matched controls [odds ratio (OR) = 2.65, 95% confidence interval (CI) = 2.07-3.40 and OR = 1.75, 95% CI = 1.17-2.61, respectively]. CONCLUSIONS: Having multiple convictions for driving under the influence of alcohol in women appears to be a risk factor for increased maternal, infant and child mortality.

2.
Drug Alcohol Depend ; 201: 147-154, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31229702

RESUMO

BACKGROUND: Alcoholism is a multifactorial disorder influenced by multiple gene loci, each with small effect. Studies suggest shared genetic influences across DSM-IV alcohol dependence symptoms, but shared effects across DSM-5 alcohol use disorder remains unknown. We aimed to test the assumption of genetic homogeneity across the 11 criteria of DSM-5 alcohol use disorder (AUD). METHODS: Data from 2596 alcohol using individuals of European ancestry from the Study of Addiction: Genetics and Environment were used to examine the genomewide SNP-heritability (h2SNP) and SNP-covariance (rGSNP) between 11 DSM-5 AUD symptoms. Phenotypic relationships between symptoms were examined to confirm an underlying liability of AUD and the SNP-heritability of the observed latent trait and the co-heritabilityamong AUD symptoms was assessed using Genomic-Relatedness-Matrix-Restricted-Maximum-Likelihood. Genetic covariance among symptoms was examined using factor analysis. RESULTS: Phenotypic relationships confirmed a unidimensional underlying liability to AUD. Factor and parallel analyses of the observed genetic variance/covariance provided evidence of genetic homogeneity. Additive genetic effects on DSM-5 AUD symptoms varied from 0.10 to 0.37 and largely overlapped (rG-SNP across symptoms ranged from 0.49 - 0.92). The additive genetic effect on the DSM-5 AUD factor was 0.36, 0.14 for DSM-5 AUD diagnosis, and was 0.22 for DSM-5 AUD severity. CONCLUSIONS: Common genetic variants influence DSM-5 AUD symptoms. Despite evidence for a common AUD factor, the evidence of only partially overlapping genetic effects across AUD symptoms further substantiates the need to simultaneously model common and symptom-specific genetic effects in molecular genetic studies in order to best characterize the genetic liability.

3.
Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101

RESUMO

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

4.
Drug Alcohol Depend ; 198: 168-175, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939374

RESUMO

BACKGROUND: Understanding differences in nicotine dependence assessments' ability to predict smoking cessation is complicated by variation in quit attempt contexts. Pregnancy reduces this variation, as each pregnant smoker receives the same strong cessation incentive. Cigarette smoking during pregnancy (SDP) provides a powerful paradigm for analyzing the interplay between nicotine dependence measures and sociodemographics in predicting cessation failure. METHODS: Data from a female twin cohort (median birth year 1980), assessed in teens and early twenties, were merged with birth records to identify those with smoking history who experienced childbirth (N = 1657 births, N = 763 mothers). Logistic regression predicting SDP, as a function of birth record sociodemographic variables, generated a sociodemographic risk-score. Further analysis incorporated the risk-score with data from research interviews on DSM-IV-Nicotine Dependence symptom count, Heaviness of Smoking Index. RESULTS: Low maternal educational level, younger age at childbirth, and being unmarried all contributed risk for SDP. In addition to sociodemographic risk-score, the best predictors of SDP included HSI-score (OR:1.51), their two-way interaction (OR:0.39; reduced impact of dependence at intermediate-high sociodemographic risk), history of ≥ two failed quit attempts (OR:1.38), and a dummy variable for prior pregnancy at time of assessment (OR:1.82). DSM-IV-Nicotine Dependence symptoms underperformed the Heaviness of Smoking Index and did not improve prediction when added to the best model. CONCLUSIONS: The 2-item Heaviness of Smoking Index measure and report of ≥ two failed quit attempts performed best for predicting SDP. The contribution of either nicotine dependence measure to SDP risk was diminished at increased levels of sociodemographic risk.

5.
Am J Med Genet B Neuropsychiatr Genet ; 180(6): 439-447, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30708398

RESUMO

Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.

6.
Nat Commun ; 10(1): 29, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30604766

RESUMO

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.


Assuntos
Taxa de Filtração Glomerular/genética , Hipertensão/genética , Cálculos Renais/genética , Rim/fisiopatologia , Insuficiência Renal Crônica/genética , Adulto , Idoso , Pressão Sanguínea/genética , Grupos Étnicos/genética , Feminino , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Código das Histonas/genética , Histonas/metabolismo , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Cálculos Renais/etnologia , Cálculos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/etnologia , Insuficiência Renal Crônica/fisiopatologia
8.
Alcohol Clin Exp Res ; 43(3): 473-482, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30589442

RESUMO

BACKGROUND: Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests (LFTs), particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical LFTs could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. METHODS: Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1,003 people who had reported excessive alcohol intake (28 drinks or more per week). A total of 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT, and AST separately in the group reporting excessive alcohol intake (N = 951) and a low-intake group reporting 14 drinks or fewer per week (N = 8,716), and compared results. RESULTS: Abnormal GGT and ALT among excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C-reactive protein, ferritin, and transferrin saturation; and with lower high-density-lipoprotein cholesterol. Abnormal AST was associated with triglycerides, ferritin, and transferrin saturation. ALT was significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409, p = 0.0076; TM6SF2, rs10401969, p = 0.0076; HSD17B13, rs10433879, p = 0.0024). CONCLUSIONS: Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload and inflammation are associated with liver enzyme abnormality in excessive drinkers.

9.
Nat Commun ; 9(1): 4774, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429480

RESUMO

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.

10.
JAMA Psychiatry ; 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30347017

RESUMO

Importance: Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). However, it is unclear whether this association results from predispositional (ie, shared genetic) factors or individual-specific factors (eg, causal processes, such as cannabis use leading to PLEs). Objectives: To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twin and nontwin sibling pairs discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects. Design, Setting, and Participants: In this cross-sectional analysis, diagnostic interviews and self-reported data were collected from 2 separate population-based samples of twin and nontwin sibling pairs. Data from the Human Connectome Project were collected between August 10, 2012, and September 29, 2015, and data from the Australian Twin Registry Cohort 3 (ATR3) were collected between August 1, 2005, and August 31, 2010. Data were analyzed between August 17, 2017, and July 6, 2018. The study included data from 1188 Human Connectome Project participants and 3486 ATR3 participants, totaling 4674 participants. Main Outcomes and Measures: Three cannabis-involvement variables were examined: frequent use (ie, ≥100 times), a DSM-IV lifetime cannabis use disorder diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin and nontwin sibling pairs discordant for cannabis use. Results: Among the 4674 participants, the mean (SD) age was 30.5 (3.2) years, and 2923 (62.5%) were female. Data on race/ethnicity were not included as a covariate owing to lack of variability within the ATR3 sample; among the 1188 participants in the Human Connectome Project, 875 (73.7%) were white. Psychotic-like experiences were associated with frequent cannabis use (ß = 0.11; 95% CI, 0.08-0.14), cannabis use disorder (ß = 0.13; 95% CI, 0.09-0.16), and current cannabis use (ß = 0.07; 95% CI, 0.04-0.10) even after adjustment for covariates. Correlated genetic factors explained between 69.2% and 84.1% of this observed association. Within discordant pairs of twins/siblings (Npairs, 308-324), Psychotic-like experiences were more common in cannabis-exposed individuals compared with their relative who used cannabis to a lesser degree (ß ≥ .23, P < .05; eg, frequent and infrequent cannabis-using relatives significantly differed, z = -5.41; P < .001). Conclusions and Relevance: Despite the strong contribution of shared genetic factors, frequent and problem cannabis use also appears to be associated with PLEs via person-specific pathways. This study's findings suggest that policy discussions surrounding legalization should consider the influence of escalations in cannabis use on traitlike indices of vulnerability, such as PLEs, which could contribute to pervasive psychological and interpersonal burden.

11.
Nat Neurosci ; 21(9): 1161-1170, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150663

RESUMO

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

12.
Addiction ; 113(11): 2073-2086, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30003630

RESUMO

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

13.
Exp Clin Psychopharmacol ; 26(4): 354-365, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29985018

RESUMO

Laboratory cue exposure investigations have demonstrated that, relative to drinkers who report a high sensitivity to the pharmacologic effects of alcohol, low-sensitivity (LS) drinkers show exaggerated neurocognitive and behavioral reactivity to alcohol-related stimuli. The current study extends this line of work by testing whether LS drinkers report stronger cravings for alcohol in daily life. Data were from an ecological momentary assessment study in which participants (N = 403 frequent drinkers) carried a palmtop computer for 21 days and responded to questions regarding drinking behavior, alcohol craving, mood states, and situational context. Initial analyses identified subjective states (positive and negative mood, cigarette craving) and contextual factors (bar-restaurant location, weekend, time of day, presence of friend, recent smoking) associated with elevated craving states during nondrinking moments. Effects for nearly all these craving correlates were moderated by individual differences in alcohol sensitivity, such that the associations between situational factors and current alcohol craving were larger among LS individuals (as determined by a questionnaire completed at baseline). Complementary idiographic analyses indicated that self-reported craving increased when the constellation of situational factors more closely resembled individuals' observed drinking situations. Again, this effect was moderated by alcohol sensitivity, with greater craving response increases among LS drinkers. The findings align with predictions generated from theory and laboratory cue exposure investigations and should encourage further study of craving and incentive processes in LS drinkers. (PsycINFO Database Record

14.
Womens Health Issues ; 28(5): 421-429, 2018 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29903544

RESUMO

BACKGROUND: Trauma exposure has been linked to risky sexual behavior (RSB), but few studies have examined the impact of distinct trauma types on RSB in one model or how the association with trauma and RSB may differ across race. PURPOSE: The objective of the current study was to examine the contribution of trauma exposure types to RSB-substance-related RSB and partner-related RSB identified through factor analysis-in young Black and White adult women. METHODS: We investigated the associations of multiple trauma types and RSB factor scores in participants from a general population sample of young adult female twins (n = 2,948). We examined the independent relationship between specific traumas and RSB, adjusting for substance use, psychopathology, and familial covariates. All pertinent constructs were coded positive only if they occurred before sexual debut. RESULTS: In Black women, sexual abuse was significantly associated with substance-related and partner-related RSB, but retained significance only for partner-related RSB in a fully adjusted model. For White women, sexual abuse and physical abuse were associated with both RSB factors in the base and fully adjusted models. Witnessing injury or death was only associated with RSBs in base models. For both groups, initiating alcohol (for Black women), alcohol, or cannabis (for White women) before sexual debut (i.e., early exposure) was associated with the greatest increased odds of RSB. CONCLUSIONS: Data highlight the contribution of prior sexual abuse to RSBs for both White and Black women, and of prior physical abuse to RSBs for White women. Findings have implications for intervention after physical and sexual abuse exposure to prevent RSB, and thus, potentially reduce sexually transmitted infection/human immunodeficiency virus infection and unintended pregnancy in young women.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Afro-Americanos/psicologia , Grupo com Ancestrais do Continente Europeu/psicologia , Assunção de Riscos , Delitos Sexuais/psicologia , Comportamento Sexual/psicologia , Parceiros Sexuais , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Feminino , Infecções por HIV , Humanos , Masculino , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
15.
Twin Res Hum Genet ; 21(3): 179-190, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29757125

RESUMO

BACKGROUND: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. METHODS: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime 'ever' smoking measure was obtained from twins and relatives in the 'Virginia 30,000' sample and the 'Australian 25,000'. RESULTS: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. CONCLUSIONS: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI.

16.
Psychol Med ; : 1-10, 2018 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-29729685

RESUMO

BACKGROUND: Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences. METHODS: Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24-42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project. RESULTS: The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37-0.81)] and women [rG = 0.56 (0.49-0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01-0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females. CONCLUSIONS: Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.

17.
Twin Res Hum Genet ; 21(3): 163-178, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29692273

RESUMO

Drinking alcohol is a normal behavior in many societies, and prior studies have demonstrated it has both genetic and environmental sources of variation. Using two very large samples of twins and their first-degree relatives (Australia ≈ 20,000 individuals from 8,019 families; Virginia ≈ 23,000 from 6,042 families), we examine whether there are differences: (1) in the genetic and environmental factors that influence four interrelated drinking behaviors (quantity, frequency, age of initiation, and number of drinks in the last week), (2) between the twin-only design and the extended twin design, and (3) the Australian and Virginia samples. We find that while drinking behaviors are interrelated, there are substantial differences in the genetic and environmental architectures across phenotypes. Specifically, drinking quantity, frequency, and number of drinks in the past week have large broad genetic variance components, and smaller but significant environmental variance components, while age of onset is driven exclusively by environmental factors. Further, the twin-only design and the extended twin design come to similar conclusions regarding broad-sense heritability and environmental transmission, but the extended twin models provide a more nuanced perspective. Finally, we find a high level of similarity between the Australian and Virginian samples, especially for the genetic factors. The observed differences, when present, tend to be at the environmental level. Implications for the extended twin model and future directions are discussed.

18.
Alcohol Clin Exp Res ; 42(3): 646-653, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29437240

RESUMO

BACKGROUND: Women are increasingly involved in drunk driving and fatal crashes, yet except for the screening performed in criminal justice settings, little is known about their life context, psychiatric histories, and family backgrounds. This study describes a sample of women with histories of arrest for driving under the influence of alcohol (DUI) who were interviewed outside a criminal justice setting and contrasts women with single versus multiple DUI convictions. METHODS: Women with recent documented histories of DUI participated in a study of women's health behaviors. Thirty-six women with 1 DUI and 62 with 2 or more DUIs participated in a diagnostic telephone interview which assessed demographics, alcohol use and problems, psychiatric problems, treatment, and partner violence. RESULTS: The sample overall had high rates of co-occurring psychiatric problems, parental alcohol problems, early sexual and physical abuse, and head injuries. Alcohol use severity and the prevalence of head injuries and partner alcohol problems were significantly higher among women with multiple DUIs than women with a single DUI. Measures reflecting life context, such as marital status, number of children, and childhood trauma, were not associated with number of DUIs. CONCLUSIONS: Findings suggest that DUI recidivism in women is accounted for primarily by AUD severity and is not influenced by previous life events such as partner violence, psychiatric problems, and family context such as divorce/separation or number of children. Multiple DUIs in women may mark an alcohol severity threshold beyond which few factors account for additional risk.

19.
Prev Sci ; 19(6): 795-804, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28875252

RESUMO

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.

20.
Addiction ; 113(1): 158-166, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28833688

RESUMO

BACKGROUND AND AIMS: Both high alcohol intake and alcohol dependence increase mortality, and both are associated with smoking. We aimed to compare the associations of quantity of alcohol, number of alcohol-related symptoms and smoking history with all-cause mortality, and to assess symptom count and smoking history as confounders or mediators of the effects of high alcohol intake. DESIGN: Survival was analysed by Cox regression with sex, body mass index, alcohol intake (overall and by beverage), maximum drinks on any day, alcohol symptom count and smoking status as potential predictors of age at death. SETTING: Australia. PARTICIPANTS: Participants were apparently healthy volunteers consisting of 33 593 Australian adult twins and their relatives who completed questionnaires or interviews between 1979 and 2005. MEASUREMENTS: Data on alcohol use, smoking and occurrence of symptoms related to alcohol use disorders and death records from the Australian National Death Index. FINDINGS: A total of 3764 participants were matched with deaths occurring within Australia up to July 2014. Individually, alcohol intake [hazard ratio (HR) = 1.0082, 95% confidence interval (CI) = 1.0063-1.0102, per drink per week], beer intake (HR = 1.0159, 95% CI = 1.0123-1.0195, per drink per week), life-time maximum number of drinks in 1 day (HR = 1.0176, 95% CI = 1.0130-1.0221, per drink), symptom count (HR = 1.0867, 95% CI = 1.0633-1.1106, per symptom) and smoking status (HR = 2.82, 95% CI = 2.52-3.16 for smokers of 10+ cigarettes/day versus never-smokers) were each significant predictors of all-cause mortality. After adjustment for the independently significant predictors alcohol symptom count and smoking status, alcohol intake was no longer significant (adjusted HR = 1.0012 per drink per week, 95% CI = 0.9979-1.0145). CONCLUSIONS: Number of symptoms related to high alcohol intake and tobacco smoking appear to account for the positive association between alcohol consumption and premature mortality.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Fumar Cigarros/epidemiologia , Mortalidade Prematura , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Cerveja , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fumar/epidemiologia , Análise de Sobrevida , Fumar Tabaco
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