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Home > Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence.

Kuo, Po-Hsiu and Neale, Michael C and Riley, Brien P and Webb, Bradley Todd and Sullivan, Patrick F and Vittum, Jen and Patterson, Diana G and Thiselton, Dawn L and Oord, Edwin J van den and Walsh, Dermot and Kendler, Kenneth S and Prescott, Carol A (2006) Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence. Alcoholism Clinical and Experimental Research , 30 , (11) , pp. 1807-1816.

Background: Alcoholism is a phenotypically and probably genetically heterogeneous condition. Thus, one strategy for finding genes influencing liability to alcoholism is to study the components of alcoholism, which may be more directly related to the underlying pathophysiology than is clinical diagnosis. The goal of this study was to identify genomic regions containing susceptibility loci for alcohol-related traits.

Methods: A 4-cM dense whole-genome linkage study was conducted in the Irish Affected Sib Pair Study of Alcohol Dependence. Probands, affected siblings, and parents were evaluated by structured interview. Variance component linkage analysis was applied to data from 485 families for 5 measures: initial sensitivity and tolerance (based on scales from the self-report of the effects of ethanol; maximum drinks within 24 hours, an empirically derived factor score based on withdrawal symptoms, and age at onset of alcohol dependence.

Results: Evidence for linkage (p<0.005) was found on 9 chromosomes. For age at onset, 2 regions were found on chromosome 9 (highest Lod = 2.3, p = 0.0005). For initial level of response to alcohol, suggestive regions were on chromosomes 1 and 11 (highest Lod = 2.9, p = 0.0001 on chromosome 11), while those for tolerance signals were on chromosomes 1, 6, and 22. Maximum drinking was associated with regions on chromosomes 12 and 18. For withdrawal symptoms, the highest peak was on chromosome 2 (Lod = 2.2, p = 0.0007).

Conclusions: Using quantitative measures of components of alcohol dependence, we identified several regions of the genome that may contain susceptibility loci for specific alcohol-related traits and merit additional study.

 

Item Type
Article
Date
November 2006
Season/Number
11
Page Range
pp. 1807-1816
Publisher
Wiley-Blackwell
Volume
30
Number
11
Keywords
alcohol-related genetic markers, genetic linkage, genetic risk factors, genetic trait, genetic variance, Ireland
EndNote
Accession Number
HRB 4212 (Available)

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