Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
16340454
TITLE
Autosomal linkage analysis for the level of response to alcohol.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
The level of response (LR) to alcohol is a genetically-influenced phenotype related to the alcoholism risk. Usually measured by evaluating psychological and physiological changes that follow the administration of alcohol, the heritability of LR is estimated to be between 0.4 and 0.6, and efforts are being made to find genes related to this phenotype. This paper presents data from a family-based genome with linkage analysis focusing on alcohol challenge determinants of LR.
METHODS NlmCategory: METHODS
The subjects were 18-to-29-year-old sibling pairs with at least one parent who was alcohol-dependent and who had experience with alcohol but were not yet alcohol-dependent themselves. Both members of the sibling pairs were given oral alcohol challenges (0.75-0.90 ml/kg of ethanol for females and males, respectively), with LR established using the Subjective High Assessment Scale (SHAS) and changes in body sway (BS) repeatedly over a 3.5-hr. period. Blood samples from siblings and at least one parent were genotyped using 811 microsatellite markers, with results evaluated using several related variance component approaches as implemented in SOLAR for continuous traits. In addition, association was tested using single nucleotide polymorphisms (SNPs) within the KCNMA1, HTR7 and SLC18A2 genes that may relate to a finding on chromosome 10.
RESULTS NlmCategory: RESULTS
Data were generated from 238 sib-pairs representing 365 individuals (41.6% were males) from 165 families. The most consistent results across methods and samples were observed for SHAS on chromosome 10 between 120 and 140 cM (with a maximum LOD score of 2.6 at 122 cM), and a second region of possible interest at 173 cM (LOD = 1.2). Statistical analysis with the KCNMA1, HTR7 and SLC18A2 genes, which lie in the support region of interest revealed no evidence for association after correction for multiple comparisons.
CONCLUSIONS NlmCategory: CONCLUSIONS
These evaluations from the largest known alcohol challenge-based genetic study to date highlight the potential importance of genes on chromosome 10 as possible contributors to the low LR to alcohol as a risk factor for alcoholism.
DATE PUBLISHED
2005 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2005/12/13 09:00
medline 2006/10/19 09:00
entrez 2005/12/13 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Schuckit MA Schuckit Marc A MA Department of Genetics and Neurology, the Carolina Center for Genome Sciences, Chapel Hill, NC, USA. mschuckit@ucsd.edu
Wilhelmsen K Wilhelmsen Kirk K
Smith TL Smith Tom L TL
Feiler HS Feiler Heidi S HS
Lind P Lind Penelope P
Lange LA Lange Leslie A LA
Kalmijn J Kalmijn Jelger J
INVESTIGATORS
JOURNAL
VOLUME: 29
ISSUE: 11
TITLE: Alcoholism, clinical and experimental research
ISOABBREVIATION: Alcohol. Clin. Exp. Res.
YEAR: 2005
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0145-6008
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Alcohol Clin Exp Res
COUNTRY: England
ISSNLINKING: 0145-6008
NLMUNIQUEID: 7707242
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AA05526 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Alcohol Drinking psychology
Alcoholism genetics
Chromosomes, Human, Pair 10 genetics
Dose-Response Relationship, Drug genetics
Ethanol pharmacology
Family pharmacology
Female pharmacology
Genetic Linkage pharmacology
Genetic Predisposition to Disease pharmacology
Humans pharmacology
Lod Score pharmacology
Male pharmacology
Microsatellite Repeats genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Postural Balance drug effects
Potassium Channels, Calcium-Activated genetics
Sex Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Potassium Channels, Calcium-Activated
3K9958V90M Ethanol
OTHER ID's