Browsing by Author "Irons, Daniel Edward"

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    Characterizing specific henetic and environmental influences on alcohol use
    (2012-09) Irons, Daniel Edward
    Although both genetic and environmental influences, as well as the interplay between them, are clearly important to the development of alcohol use and related psychopathology, the effects of many of the particular genetic variants and environmental risk factors responsible have not yet been confirmed. We conducted three studies with the goal of moving beyond abstract estimates of genetic and environmental variance to the assessment of whether specified risk factors were causally implicated in the development of alcohol-related behaviors and problems. First, in a longitudinally assessed sample of 356 adopted adolescents and young adults of East Asian descent, we examined the progression over time of the relationship between a functional polymorphism in the alcohol metabolism gene aldehyde dehydrogenase 2 (ALDH2) and multiple measures of drinking behavior. We found that the protective effect of the less-functional ALDH2 variant increased between mid-adolescence and early adulthood, and that non-biological parental alcohol use, but not sibling alcohol use, nor deviant peer affiliation, moderated the effect of the gene. In a second study, using a community-based sample of 7224 individuals assessed in early and middle adulthood, we employed multiple methods to conduct a comprehensive examination of the effects of markers in GABA system genes on measures of alcohol use and related symptomatology. We tested not only the potential effects of individual markers, but also their effects in aggregate, and at the whole-gene and system-wide levels. None of these methods produced results indicative of an effect of GABA system variants on measures of alcohol use or misuse. We conducted a third study with a sample of 1512 twins, longitudinally assessed from early adolescence into adulthood, to determine whether adult alcohol use and misuse, as well as other adult outcomes, could be attributed to the causal effect of alcohol exposures in early adolescence. We used two separate techniques to adjust for potentially confounding factors. First, we used a propensity score design to adjust for the potentially confounding effects of a number of measured background covariates. Second, we used the cotwin control design to adjust for confounding due to unmeasured factors (including genetic influences) shared between twins in pairs discordant for early alcohol exposure. The results of both methods applied in this third study were generally consistent with there being a causal effect of early alcohol exposures on the later development of adult alcohol problems and other related adult outcomes, but contrasting the two methods indicated that exposure effect estimates from the propensity score application were likely to be biased by unmeasured confounding variables. In summary, we have first substantially elaborated upon the effects of a genetic variant known to influence alcohol-related behaviors (in the ALDH2 gene); next, despite thorough investigation, we have found no evidence for the effects of a second set of purported genetic influences (GABA system genes); and finally, we provided evidence that early alcohol exposure likely exerts a genuinely causal influence on later alcohol-related problems and other adult outcomes.
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    Polymorphisms in Dopamine System Genes DAT1 and DRD4 are Associated with Disinhibitory Psychopathology in Adolescence
    (2009-10) Irons, Daniel Edward
    The specificity of genetic influence upon childhood disorders of behavioral disinhibition is uncertain. Polymorphisms in dopamine system genes have been implicated in the contribution of risk for attention-deficit/hyperactivity disorder (ADHD), and other externalizing behavior disorders, but the range of behaviors affected by variation in these genes is ambiguous. To address this problem, we examined the relationship between polymorphisms in the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes and the symptoms and diagnoses of ADHD, ADHD subtypes, oppositional defiant disorder (ODD), and conduct disorder (CD) in 2902 individuals from a population-based twin sample. We observed an association between risk alleles in both DAT1 and DRD4 polymorphisms and increased risk for ADHD, but no main effects of variation in these genes upon risk for ODD or CD. Furthermore, the risk contributed by DAT1 and DRD4 to ADHD was not general; risk alleles in each gene were associated with specific patterns of changes in ADHD subtypes and symptom dimensions.