Genomewide Association Study of Alcohol Use and Alcohol Use Disorder in Australian Twin-Families (OZ-ALC GWAS)

The Australian twin-family study of alcohol use disorder (OZALC study) derives from telephone diagnostic interview studies of two general population volunteer cohorts of Australian twins (cohort 1, mostly born 1940-1964; cohort 2, born 1964-71) and the spouses of the former cohort - a total of over 11,000 families. Three coordinated studies, using a shared assessment protocol and with a shared goal of gene-discovery, were conducted - one funded by the National Institute on Drug Abuse, the others by the National Institute on Alcoholism and Alcohol Abuse - by investigators associated with the Midwest Alcoholism Research Center at Washington University in St. Louis, and investigators at Queensland Institute of Medical Research, Brisbane, Australia (led by Professor Nicholas Martin), using informative families identified from these cohorts. The first of these (NIDA Nicotine Addiction Genetics [NAG] project, PI Pamela Madden) identified index cases from the 3 cohorts with a history of heavy smoking (smoked 20 or more cigarettes daily, or 40 or more cigarettes on 1 or more occasions) and with additional available full siblings who were smokers, and interviewed and obtained blood samples from twins, and cooperative full siblings and parents, in order to identify families that would be informative for linkage analysis of a quantitative heaviness of smoking trait. The second identified additional families with an index case who either reported a history of alcohol dependence (DSM-IV), or scored above the 85th percentile on a quantitative measure of heaviness of alcohol use (alcohol factor score), derived from measures of frequency of heavy drinking, frequency of drinking to intoxication, and typical weekly consumption in standard drinks (all referenced to the respondent's heaviest drinking period) and of lifetime maximum 1-day alcohol consumption and maximum tolerance to alcohol (drinks before getting drunk or before feeling effects of alcohol). Interview and DNA were obtained from index cases and siblings, and DNA only from available parents. The goal of this second study (NIAAA OZ-ALCOHOL EDAC study, PI Andrew Heath) was to identify sibships including pairs who were either extreme concordant for the quantitative consumption measure (both scoring above the 85th percentile) or extreme discordant (one scoring above the 85th percentile and one scoring below the 30th percentile) that would be informative for linkage analysis. The third identified additional sibships solely on the basis of large sibship size, regardless of alcohol or tobacco use phenotypes (NIAAA OZ-BIGSIB study, PIs the late Richard Todd, Andrew Heath). From these coordinated studies a case-control series of alcohol dependent individuals and unaffected controls were constructed for a family-based Genomewide Association Study (OZALC-GWAS) of heaviness of alcohol use and alcohol dependence, funded by the National Institute of Alcoholism and Alcohol Abuse. These data are made available here for all investigators studying outcomes related to alcohol or tobacco use (including major depressive disorder).

• Study Weblinks:
  • Midwest Alcoholism Research Center
• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Twin
  • Family
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 6775
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• PMC

Family-based sampling design with presence or absence of history of alcohol dependence used to define case versus control status.

• Primary Phenotype: Alcohol-Related Disorders
• Tobacco Use Disorder
• Depressive Disorder

• Principal Investigator, OZALC-EDAC Project (2001-2008)
  • Andrew C. Heath, DPhil. Washington University School of Medicine, St. Louis, MO, USA (Lead Institution).
• Principal Investigator, OZALC-BIGSIB Project (2008-2009)
  • Andrew C. Heath, DPhil. Washington University School of Medicine, St. Louis, MO, USA (Lead Institution).
• Principal Investigator, OZALC-BIGSIB Project (2002-2008, deceased)
  • Richard D. Todd, PhD, MD. Washington University School of Medicine, St. Louis, MO, USA (Lead Institution).
• Principal Investigator, NAG Project (1999-2009)
  • Pamela A. Madden, PhD. Washington University School of Medicine, St. Louis, MO, USA (Lead Institution).
• Co-Investigator and Project Statistician, OZALC-BIGSIB Project
  • Alexandre Todorov, PhD. Washington University School of Medicine, St. Louis, MO, USA (Lead Institution).
• Site Principal Investigator, NAG, OZALC-EDAC and OZALC-BIGSIB Projects
  • Nicholas G. Martin, PhD. Queensland Institute of Medical Research, Brisbane, Australia (Data-Collection Site).
• Co-Principal Investigator and Site Molecular Geneticist, NAG, OZALC-EDAC and OZALC-BIGSIB Projects
  • Grant Montgomery, PhD. Queensland Institute of Medical Research, Brisbane, Australia (Data-Collection Site).
• Co-Principal Investigator and Site Clinical Biochemist, NAG, OZALC-EDAC and OZALC-BIGSIB Projects
  • John Whitfield, PhD. Queensland Institute of Medical Research, Brisbane, Australia (Data-Collection Site).
• Genotyping Center
  • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA.
  • DeCODE Genetics, Reykjavik, Iceland.
• Funding Source for CIDR Genotyping
  • HHSN268200782096C. NIH contract "High throughput genotyping for studying the genetic contributions to human disease". National Institutes of Health, Bethesda, MD, USA.