The search for genes related to a low-level response to alcohol determined by alcohol challenges

Kirk C. Wilhelmsen, Marc Schuckit, Tom L. Smith, James V. Lee, Samantha K. Segall, Heidi S. Feiler, Jelger Kalmijn

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


Background: A low level of response (LR) to alcohol seems to relate to a substantial proportion of the risk for alcoholism and to have significant heritability. Methods: This report describes the results of a genome-wide segregation analysis for the first 139 pairs of full siblings by using an alcohol challenge protocol as a direct measure of LR. Subjects from 18 to 29 years old were selected if the original screen indicated they had an alcohol-dependent parent, reported a personal history of drinking but had no evidence of alcohol dependence, and had a full sibling with similar characteristics. Body sway and Subjective High Assessment Scale scores were measured at baseline and at regular intervals after the administration of a measured dose of alcohol. Participants and available parents were genotyped for 811 microsatellite markers, and resulting data were analyzed with a variance component method. Results: Nine chromosome regions with logarithm of the odds ratio (LOD) between 2.2 and 3.2 were identified; several had previously been implicated regarding phenotypes relevant to alcoholism and the LR to alcohol. Several regions identified in the previous linkage study by using a retrospective self-report questionnaire were potentially confirmed by this study. The strongest evidence was on chromosomes 10, 11, and 22. Conclusions: Several chromosomal areas seem to relate to the low LR to alcohol as a risk factor for alcohol dependence.

Original languageEnglish (US)
Pages (from-to)1041-1047
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Issue number7
StatePublished - Jul 1 2003
Externally publishedYes


  • Alcohol
  • Genetics
  • Level of Response
  • Linkage

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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