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Genetic Liability (genetic + liability)
Selected AbstractsEarly cannabis use and DSM-IV nicotine dependence: a twin studyADDICTION, Issue 11 2008Arpana Agrawal ABSTRACT Background Evidence suggests that cannabis users are at increased risk for cigarette smoking,if so, this may potentially be the single most alarming public health challenge posed by cannabis use. We examine whether cannabis use prior to age 17 years is associated with an increased likelihood of DSM-IV nicotine dependence and the extent to which genetic and environmental factors contribute to this association. Methods A population-based cohort of 24,36-year-old Australian male and female twins (n = 6257, 286 and 229 discordant pairs) was used. The co-twin,control method, with twin pairs discordant for early cannabis use, was used to examine whether, after controlling for genetic and familial environmental background, there was evidence for an additional influence of early cannabis use on DSM-IV nicotine dependence. Bivariate genetic models were fitted to the full data set to quantify the genetic correlation between early cannabis use and nicotine dependence. Results The early cannabis-using twin was about twice as likely to report nicotine dependence, when compared to their co-twin who had experimented with cigarettes but had never used cannabis. Even when analyses were restricted to cannabis users, earlier age cannabis use onset conferred greater risk (1.7) for nicotine dependence than did later onset. This association was governed largely by common genetic liability to early cannabis use and nicotine dependence, as demonstrated by genetic correlations of 0.41,0.52. Conclusions Early-onset cannabis users are at increased risk for nicotine dependence, but this risk is attributable largely to common genetic vulnerability. There is no evidence for a causal relationship between cannabis use and nicotine dependence. [source] Familial loading in specific language impairment: patterns of differences across proband characteristics, gender and relative typeGENES, BRAIN AND BEHAVIOR, Issue 3 2007G. Conti-Ramsden There is now little doubt that both environmental factors and genes are likely to make important contributions to the aetiology of specific language impairment (SLI). The most commonly proposed model for understanding these influences is the multifactorial model. In the present study we examine two expectations based on this model: that there will be a systematic relationship between the severity of proband language scores and the rate and severity of SLI in relatives and that relatives will be more strongly affected if they are relatives of a proband of the more rarely affected gender (female) because the latter require a higher genetic liability to become equally impaired. Ninety-three probands and their 300 first-degree relatives participated in this study. Results showed a relationship between proband severity at age 14 and an increased rate of SLI in relatives. This relationship was strong for child siblings and was significant with respect to both rate of SLI and severity over a range of language and literacy measures. In contrast, higher levels of SLI among relatives of female rather than male probands was entirely disproved. [source] Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: Genetic linkage analysis and FISH studiesGENES, CHROMOSOMES AND CANCER, Issue 3 2004Karen L. Gross Recently, germline mutations of the fumarate hydratase (FH) gene, in 1q42.1, have been found to be involved in syndromes associated with uterine leiomyomas (ULs). Compelling evidence also supports a genetic liability to develop nonsyndromic UL, although susceptibility genes have not been reported to date. Loss of heterozygosity (LOH) studies have found no or rare evidence of LOH of FH in nonsyndromic UL. However, the karyotypes of these tumors were not reported, and cytogenetic aberrations of 1q42,44 have been observed infrequently in UL. To determine whether FH mutations also may predispose women to developing nonsyndromic UL, we performed a genetic linkage study with DNA from 123 families containing at least one affected sister pair. In addition, to assess the frequency of FH loss specifically in UL with 1q rearrangements, we performed a fluorescence in situ hybridization (FISH) analysis of UL with 1q rearrangements. Analysis of the genotyping data revealed evidence suggestive of linkage to the FH region among study participants who were less than 40 years of age at diagnosis (Zlr 1.7 at D1S547, P = 0.04). FISH results showed that one copy of FH was absent in 9 of 11 ULs. These data indicate that loss of FH might be a significant event in the pathogenesis of a subset of nonsyndromic ULs. © 2004 Wiley-Liss, Inc. [source] Common Genetic Contributions to Alcohol and Cannabis Use and Dependence SymptomatologyALCOHOLISM, Issue 3 2010Carolyn E. Sartor 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. [source] Mismatch Negativity: No Difference Between Controls and Abstinent AlcoholicsALCOHOLISM, Issue 1 2004George Fein Abstract: Background: A number of studies have examined the amplitude of the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. The current study examined MMN in alcoholics abstinent an average of 6.7 years (with a minimum of six months abstinence) compared to controls. This study examined the association of MMN with alcoholism family history density, with indices of the presence and severity of externalizing disorders (a risk-factor for alcoholism), and with alcohol use variables. Methods: Electroencephalograms were gathered on 76 subjects (38 controls, 38 abstinent alcoholics) during a nonattending mismatch negativity experiment. Measures of alcoholism family history density, disinhibited personality traits, and antisocial symptoms served as measures of risk-factors known to be associated with a genetic liability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. Results: There were no differences in MMN amplitude or latency between controls and abstinent alcoholics. There also were no significant associations between MMN measures and the measures of risk for alcoholism or with the severity of alcohol use or duration of abstinence. Conclusions: The results suggest that MMN is neither affected in chronic alcoholics nor associated with alcoholism vulnerability, and thus does not reflect a trait marker of alcoholism or alcoholism risk. The current results do not address effects on MMN of acute alcohol ingestion or withdrawal from alcohol. [source] Comorbidity of Alcohol Dependence With Attention-Deficit Hyperactivity Disorder: Differences in Phenotype With Increased Severity of the Substance Disorder, but Not in Genotype (Serotonin Transporter and 5-Hydroxytryptamine-2c Receptor)ALCOHOLISM, Issue 10 2003Monika Johann Background: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. Methods: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. Results: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. Conclusions: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence. [source] Heritability of different measures of smooth pursuit eye tracking dysfunction: A study of normal twinsPSYCHOPHYSIOLOGY, Issue 6 2000Joanna Katsanis Research studies have found that smooth pursuit eye movement dysfunction may serve as an index of genetic liability to develop schizophrenia. The heritability of various measures of smooth pursuit eye tracking proficiency and the saccades that occur during smooth pursuit was examined in 64 monozygotic (MZ) and 48 dizygotic (DZ) twin pairs. Two age cohorts were assessed (11,12 and 17,18 years of age). Intraclass correlations indicated significant similarity in the MZ twins for almost all measures in both age cohorts, whereas few of the DZ twin correlations attained significance. Biometrical modeling indicated that genetic mechanisms influence performance on both global and specific eye tracking measures, accounting for about 40% to 60% of the variance. These findings suggest that the underlying brain systems responsible for smooth pursuit and saccade generation during pursuit are under partial genetic control. [source] Genetic and environmental influences on the transmission of parental depression to children's depression and conduct disturbance: an extended Children of Twins studyTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 6 2010Judy L. Silberg Background:, Despite the increased risk of depression and conduct problems in children of depressed parents, the mechanism by which parental depression affects their children's behavioral and emotional functioning is not well understood. The present study was undertaken to determine whether parental depression represents a genuine environmental risk factor in children's psychopathology, or whether children's depression/conduct can be explained as a secondary consequence of the genetic liability transmitted from parents to their offspring. Methods:, Children of Twins (COT) data collected on 2,674 adult female and male twins, their spouses, and 2,940 of their children were used to address whether genetic and/or family environmental factors best account for the association between depression in parents and depression and conduct problems in their children. Data collected on juvenile twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) were also included to estimate child-specific genetic and environmental influences apart from those effects arising from the transmission of the parental depression itself. The fit of alternative Children of Twin models were evaluated using the statistical program Mx. Results:, The most compelling model for the association between parental and juvenile depression was a model of direct environmental risk. Both family environmental and genetic factors accounted for the association between parental depression and child conduct disturbance. Conclusions:, These findings illustrate how a genetically mediated behavior such as parental depression can have both an environmental and genetic impact on children's behavior. We find developmentally specific genetic factors underlying risk to juvenile and adult depression. A shared genetic liability influences both parental depression and juvenile conduct disturbance, implicating child conduct disturbance (CD) as an early indicator of genetic risk for depression in adulthood. In summary, our analyses demonstrate differences in the impact of parental depression on different forms of child psychopathology, and at various stages of development. [source] Social-cognition and the broad autism phenotype: identifying genetically meaningful phenotypesTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 1 2007Molly Losh Background:, Strong evidence from twin and family studies suggests that the genetic liability to autism may be expressed through personality and language characteristics qualitatively similar, but more subtly expressed than those defining the full syndrome. This study examined behavioral features of this ,broad autism phenotype' (BAP) in relation to performance on a measure of social-cognition in an attempt to tease out this complex clinical picture and identify markers of underlying neuropsychological systems of genetic significance to autism. We hypothesized that mild social-cognitive impairment would be associated with clinically defined social characteristics of the BAP (aloof personality style, lower quality social relationships, and impaired pragmatic language use). Method:, Forty-eight parents of individuals with autism (13 of whom were identified as ,aloof'), and 22 control parents, were administered the ,Eyes Test', a social-cognitive measure that taps the ability to read complex psychological states from viewing only the eye region of faces. Results:, Whereas social-cognitive ability was unimpaired among parents of autistic children in general, the subgroup of parents defined as ,aloof' displayed significant social-cognitive deficits on the ,Eyes Test'. Impaired social-cognitive ability was associated with low quality of friendships and problems with pragmatic language use, associations which mirror those documented in autism. Conclusions: Findings suggest that social-cognitive impairments co-segregate with conceptually related personality, social, and language features that constitute the BAP, and point towards performance on the Eyes Test as a genetically meaningful endophenotype. [source] Language abilities of siblings of children with autismTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 6 2003Tammy Pilowsky Background: Language abilities of siblings of children with autism were examined to explore the possibility that language abilities are behavioral markers specific to the genetic liability for autism, as part of the broader phenotype. Method: Language abilities were compared among 27 siblings of children with autism, 23 siblings of children with mental retardation of unknown etiology (MR), and 22 siblings of children with developmental language disorders (DLD). Groups were matched by siblings' age, gender, birth order, family size, ethnicity, family income and by probands' gender and mental age. Results: Siblings of children with autism achieved higher scores than siblings of children with DLD on receptive, expressive, and total language scales of the Children's Evaluation of Language Fundamentals and on verbal IQ. Moreover, within the DLD group, school problems in the domains of reading and arithmetic were more prevalent than within the other two groups. Only 2 siblings of children with autism received clinical diagnoses based on DSM-IV criteria compared to 3 siblings of children with MR and 7 siblings of children with DLD. Conclusions: After excluding data of the diagnosed siblings, no differences in language abilities could be discerned among the groups, except that more siblings in the DLD group were identified as having language difficulties. In summary, although language deficits characterize autism, siblings of children with autism were not found to demonstrate deficits in language skills assessed by formal language tests, IQ, or academic skills. [source] | |||||||||||||