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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.

ABSTRACT: Twin studies provide strong evidence that there is a shared genetic liability that predisposes to a number of different psychiatric outcomes related to behavioral disinhibition. Further, alcohol dependence comorbid with other disinhibitory disorders is particularly heritable. Chromosome 2p14-2q14.3 has been linked to multiple psychiatric conditions related to behavioral undercontrol. In the Collaborative Study on the Genetics of Alcoholism (COGA), we previously reported linkage to this region with alcohol dependence (AD), suicide attempts (SUI), and conduct disorder (CD). In this study, we follow-up on these previous reports of linkage by combining the phenotypes in analyses that jointly consider the presence of multiple conditions. Linkage analyses of the combined phenotype of AD with CD or SUI results in a maximum LOD score of 5.4 in this region. In addition to this primary linkage peak, independent samples have reported linkage to other alcohol-related phenotypes across chromosome 2. Accordingly, we followed-up these linkage signals by testing for association with SNPs across chromosome 2 in a case-control sample, in which a subset of the cases consisted of alcohol-dependent probands from the linkage sample. We find evidence of association with the combined AD with CD or SUI phenotype, with 23 genes surviving permutation testing. The number of associated genes across the chromosome may explain the persistent linkage findings reported on chromosome 2 across a number of independent studies of alcohol and disinhibitory phenotypes. Further, none of the genes were located directly under the primary COGA linkage peak, which has implications for association tests following-up linkage peaks.

SUBMITTER: Dick DM

PROVIDER: S-EPMC3597340 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.

Dick Danielle M DM Meyers Jacquelyn J Aliev Fazil F Nurnberger John J Kramer John J Kuperman Sam S Porjesz Bernice B Tischfield Jay J Edenberg Howard J HJ Foroud Tatiana T Schuckit Marc M Goate Alison A Hesselbrock Victor V Bierut Laura L

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20100901 6

Twin studies provide strong evidence that there is a shared genetic liability that predisposes to a number of different psychiatric outcomes related to behavioral disinhibition. Further, alcohol dependence comorbid with other disinhibitory disorders is particularly heritable. Chromosome 2p14-2q14.3 has been linked to multiple psychiatric conditions related to behavioral undercontrol. In the Collaborative Study on the Genetics of Alcoholism (COGA), we previously reported linkage to this region wi ...[more]

PMID: 20468071

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Project description:We conducted a retrospective investigation of potential clinical, demographic, and neuropsychological risk factors for suicide attempts in patients diagnosed with bipolar disorder.Participants included 67 adult inpatients and outpatients aged 18-60 years meeting DSM-IV criteria for bipolar disorder (bipolar I and II disorders, bipolar disorder not otherwise specified). We assessed demographic factors, mood symptoms, psychosis, trauma history, trait impulsivity, trait aggression, and reasons for living. The primary outcome measures were the Barratt Impulsiveness Scale-version II, Aggression Questionnaire, and 10 cognitive outcome variables. The cognitive outcome variables assessed cognitive performance across several domains, including processing speed, attention, verbal learning, and executive function. Another aspect of cognitive function, decision making, was assessed using the Iowa Gambling Task. The study was conducted from July 2007-July 2009.We found that nonattempters reported significantly higher trait impulsivity scores on the Barratt Impulsiveness Scale compared to attempters (t(57) = 2.2, P = .03) and that, among attempters, lower trait impulsivity score was associated with higher scores of lethality of prior attempts (r(25) = -0.53, P = .01). Analyses revealed no other group differences on demographic, clinical, or neurocognitive variables when comparing attempters versus nonattempters. Regression models failed to identify any significant predictors of past suicide attempt.The largely negative results of our study are particularly important in highlighting the clinical dilemma faced by many clinicians when trying to predict which patients will make serious suicide attempts and which patients are at a lower risk for acting on suicidal thoughts. A limitation of our work is that we examined stable trait measures of impulsivity among a euthymic sample rather than mood state or the impact of mood state on traits. Overall, we conclude that suicidal behavior is extremely difficult to predict, even when comprehensive clinical and neurocognitive information is available.

Project description:BackgroundWomen who give birth to children with fetal alcohol spectrum disorder (FASD) may be at increased risk for suicide; however, there are few data in this area. The objective of this study was to compare rates of suicide between women who had given birth to children with FASD and women who had not given birth to children with FASD during critical periods in their lives, including before pregnancy, during pregnancy, during the postpartum period (maternal death) and until the end of the study period.MethodsWe conducted a retrospective cohort analysis of women with children born in Manitoba between Apr. 1, 1984, and Mar. 31, 2012 in whom FASD was diagnosed between Apr. 1, 1999, and Mar. 31, 2012, with follow-up until Dec. 1, 2013 (FASD group; n = 702). We generated a comparison group of women who had not given birth to children with FASD (n = 2097), matched up to 1:3 on date of birth of the index child, socioeconomic status and region of residence. We used linked administrative data to investigate suicide attempt and completion rates in the 2 groups. Regression modelling produced relative rates (RRs) adjusted for socioeconomic status and age at birth of the index child and was used to assess suicide risk.ResultsThe 2799 participants produced 40 390.21 person-years until the end of the study period. Compared to the comparison group, the FASD group had higher rates of suicide completion (adjusted RR 6.20 [95% confidence interval (CI) 2.36-16.31]), a higher number of women who attempted suicide after the postpartum period until the end of the study period (adjusted RR 4.62 [95% CI 2.53-8.43]) and a higher number of attempts after the postpartum period until the end of the study period (adjusted RR 3.92 [95% CI 2.30-6.09]).InterpretationThis study identified a group of women with increased rates of social complexities, mental disorders and alcohol use, which places them at risk for suicide. Interventions are needed that screen for suicidal behaviour in women who are at high risk to consume alcohol during pregnancy and have mental disorders.

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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.

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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.

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