Dataset Information

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

ABSTRACT: The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10-6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

SUBMITTER: Treutlein J

PROVIDER: S-EPMC5541316 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

Treutlein Jens J Frank Josef J Streit Fabian F Reinbold Céline S CS Juraeva Dilafruz D Degenhardt Franziska F Rietschel Liz L Witt Stephanie H SH Forstner Andreas J AJ Ridinger Monika M Strohmaier Jana J Wodarz Norbert N Dukal Helene H Foo Jerome C JC Hoffmann Per P Herms Stefan S Heilmann-Heimbach Stefanie S Soyka Michael M Maier Wolfgang W Gaebel Wolfgang W Dahmen Norbert N Scherbaum Norbert N Müller-Myhsok Bertram B Lucae Susanne S Ising Marcus M Stickel Felix F Berg Thomas T Roggenbuck Ulla U Jöckel Karl-Heinz KH Scholz Henrike H Zimmermann Ulrich S US Buch Stephan S Sommer Wolfgang H WH Spanagel Rainer R Brors Benedikt B Cichon Sven S Mann Karl K Kiefer Falk F Hampe Jochen J Rosendahl Jonas J Nöthen Markus M MM Rietschel Marcella M

Genes 20170717 7

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10-6; p<sub ...[more]

PMID: 28714907

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Project description:A considerable economic burden has been repeatedly associated with alcohol dependence (AD) - mostly calculated using aggregate data and alcohol-attributable fractions (top-down approach). However, this approach is limited by a number of assumptions, which are hard to test. Thus, cost estimates should ideally be validated with studies using individual data to estimate the same costs (bottom-up approach). However, bottom-up studies on the economic burden associated with AD are lacking. Our study aimed to fill this gap using the bottom-up approach to examine costs for AD, and also stratified the results by the following subgroups: sex, age, diagnostic approach and severity of AD, as relevant variations could be expected by these factors.1356 primary health care patients, representative for two German regions. AD was diagnosed by a standardized instrument and treating physicians. Individual costs were calculated by combining resource use and productivity data representing a period of six months prior to the time of interview, with unit costs derived from the literature or official statistics. The economic burden associated with AD was determined via excess costs by comparing utilization of various health care resources and impaired productivity between people with and without AD, controlling for relevant confounders. Additional analyses for several AD characteristics were performed.Mean costs among alcohol dependent patients were 50 % higher compared to the remaining patients, resulting in 1836 € excess costs per alcohol dependent patient in 6 months. More than half of these excess costs incurred through increased productivity loss among alcohol dependent patients. Treatment for alcohol problems represents only 6 % of these costs. The economic burden associated with AD incurred mainly among males and among 30 to 49 year old patients. Both diagnostic approaches were significantly related to the economic burden, while costs increased with alcohol use disorder severity but not with other AD severity indicators.Our study confirms previous studies using top-down approaches to estimate the economic burden associated with AD. Further, we highlight the need for efforts aimed at preventing adverse outcomes for health and occupational situation associated with alcohol dependence based on factors associated with particularly high economic burden.

Project description:The present study examined the association between personality pathology (PP) and alcohol dependence (AD; both lifetime and in the past 12 months) among middle-aged to older adults incorporating three sources of assessment, specifically, diagnostic interviews as well as self- and informant reports. We collected data from a representative sample of community participants (N = 1,630; ages 54-65 years) and their informants (N = 1,462). Measures employed were the substance use disorder sections of the Mini-International Neuropsychiatric Interview Schedule for Mental Disorders, the Structured Interview for DSM-IV Personality (American Psychiatric Association, 2000, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev.; DSM-IV-TR SIDP) and the NEO-Personality Inventory-Revised (Costa, P. T., & McCrae, R. R., Revised NEO-Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) manual, 1992, Odessa, FL, Psychological Assessment Resources; self-report and informant versions). To complement the diagnostic interview for personality disorders (PDs), we utilized a PD-count technique derived from the five-factor model (FFM), which provided an index of PP liability. Factors representing lifetime and past-12 month AD were regressed on each of the 10 PP factors constructed from the SIDP interview, as well as self-report and informant FFM-count scores. Lifetime diagnosis of AD was positively associated with higher scores on several PP measures, including paranoid, schizotypal, antisocial, borderline, histrionic, and narcissistic PP. There was an inverse relation between lifetime AD and the factor score for obsessive-compulsive PP. With regard to AD in the past 12 months, antisocial, borderline, histrionic, and narcissistic PP factors were significantly associated with increased risk for AD, whereas the obsessive-compulsive and schizoid PP factors were associated with decreased risk for AD. The present data indicate that features of antisocial and borderline PP continue to exhibit a relatively strong association with risk for AD in later middle age.

Dataset Information

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

Publications

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

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