Dataset Information

Linkage analysis of alcohol dependence symptoms in the community.

ABSTRACT: BACKGROUND:We have previously identified suggestive linkage for alcohol consumption in a community-based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms. METHODS:An alcohol dependence symptom score, based on DSM-IIIR and DSM-IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518 females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed on 2 occasions, approximately 10 years apart. Linkage analyses were conducted on datasets compiled to maximize data collected at either the younger or the older age. In addition, linkage was compared between full samples and truncated samples that excluded the lightest drinkers (approximately 10% of the sample). RESULTS:Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously identified in alcohol linkage studies using clinical populations. Linkage signal strength was found to vary between full and truncated samples and when samples differed only on the collection age for a sample subset. CONCLUSIONS:The results support the finding that large community samples can be informative in the study of alcohol-related traits.

SUBMITTER: Hansell NK

PROVIDER: S-EPMC3210700 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Linkage analysis of alcohol dependence symptoms in the community.

Hansell Narelle K NK Agrawal Arpana A Whitfield John B JB Morley Katherine I KI Gordon Scott D SD Lind Penelope A PA Pergadia Michele L ML Montgomery Grant W GW Madden Pamela A F PA Todd Richard D RD Heath Andrew C AC Martin Nicholas G NG

Alcoholism, clinical and experimental research 20091023 1

<h4>Background</h4>We have previously identified suggestive linkage for alcohol consumption in a community-based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms.<h4>Methods</h4>An alcohol dependence symptom score, based on DSM-IIIR and DSM-IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518 females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed on 2 occa ...[more]

PMID: 19860796

Similar Datasets

Project description:BACKGROUND:While genetic influences on alcohol dependence (AD) are substantial, progress in the identification of individual genetic variants that impact on risk has been difficult. METHODS:We performed a genome-wide association study on 3,169 alcohol consuming subjects from the population-based Molecular Genetics of Schizophrenia (MGS2) control sample. Subjects were asked 7 questions about symptoms of AD which were analyzed by confirmatory factor analysis. Genotyping was performed using the Affymetrix 6.0 array. Three sets of analyses were conducted separately for European American (EA, n = 2,357) and African-American (AA, n = 812) subjects: individual single nucleotide polymorphisms (SNPs), candidate genes and enriched pathways using gene ontology (GO) categories. RESULTS:The symptoms of AD formed a highly coherent single factor. No SNP approached genome-wide significance. In the EA sample, the most significant intragenic SNP was in KCNMA1, the human homolog of the slo-1 gene in C. Elegans. Genes with clusters of significant SNPs included AKAP9, phosphatidylinositol glycan anchor biosynthesis, class G (PIGG), and KCNMA1. In the AA sample, the most significant intragenic SNP was CEACAM6 and genes showing empirically significant SNPs included KCNQ5, SLC35B4, and MGLL. In the candidate gene based analyses, the most significant findings were with ADH1C, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) and ankyrin repeat and kinase domain containing 1 (ANKK1) in the EA sample, and ADH5, POMC, and CHRM2 in the AA sample. The ALIGATOR program identified a significant excess of associated SNPs within and near genes in a substantial number of GO categories over a range of statistical stringencies in both the EA and AA sample. CONCLUSIONS:While we cannot be highly confident about any single result from these analyses, a number of findings were suggestive and worthy of follow-up. Although quite large samples will be needed to obtain requisite power, the study of AD symptoms in general population samples is a viable complement to case-control studies in identifying genetic risk variants for AD.

Project description:Co-twin comparisons address familial confounding by controlling for genetic and environmental influences that twin siblings share. We applied the co-twin comparison design to investigate associations of adolescent factors with alcohol dependence (AD) symptoms. Participants were 1286 individuals (581 complete twin pairs; 42% monozygotic; and 54% female) from the FinnTwin12 study. Predictors included adolescent academic achievement, substance use, externalizing problems, internalizing problems, executive functioning, peer environment, physical health, relationship with parents, alcohol expectancies, life events, and pubertal development. The outcome was lifetime AD clinical criterion count, as measured in young adulthood. We examined associations of each adolescent domain with AD symptoms in individual-level and co-twin comparison analyses. In individual-level analyses, adolescents with higher levels of substance use, teacher-reported externalizing problems at age 12, externalizing problems at age 14, self- and co-twin-reported internalizing problems, peer deviance, and perceived difficulty of life events reported more symptoms of AD in young adulthood (ps < .044). Conversely, individuals with higher academic achievement, social adjustment, self-rated health, and parent-child relationship quality met fewer AD clinical criteria (ps < .024). Associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, self-rated health, and AD symptoms were of a similar magnitude in co-twin comparisons. We replicated many well-known adolescent correlates of later alcohol problems, including academic achievement, substance use, externalizing and internalizing problems, self-rated health, and features of the peer environment and parent-child relationship. Furthermore, we demonstrate the utility of co-twin comparisons for understanding pathways to AD. Effect sizes corresponding to the associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, and self-rated health were not significantly attenuated (p value threshold = .05) after controlling for genetic and environmental influences that twin siblings share, highlighting these factors as candidates for further research.

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

Linkage analysis of alcohol dependence symptoms in the community.

Publications

Linkage analysis of alcohol dependence symptoms in the community.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets