TY - JOUR
T1 - Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study
AU - Gizer, Ian R.
AU - Ehlers, Cindy L.
AU - Vieten, Cassandra
AU - Seaton-Smith, Kimberly L.
AU - Feiler, Heidi S.
AU - Lee, James V.
AU - Segall, Samantha K.
AU - Gilder, David A.
AU - Wilhelmsen, Kirk C.
N1 - Funding Information:
Funding for this study was provided by the State of California for medical research on alcohol and substance abuse through the University of California at San Francisco . Additional support was provided by the Ernest Gallo Clinic and Research Center (K.C.W.), AA10201 and U54 RR02502024 (C.L.E.), and T32 AA007573 (I.R.G.). These agencies had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.
PY - 2011/1/15
Y1 - 2011/1/15
N2 - Ample data suggest that alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31-p36.22, 2q37.3, 8q24.3, and 18p11.21-p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31-p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3-p24.1, 9p24.1-p23, and 22q12.3-q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence.
AB - Ample data suggest that alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31-p36.22, 2q37.3, 8q24.3, and 18p11.21-p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31-p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3-p24.1, 9p24.1-p23, and 22q12.3-q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence.
KW - Addiction
KW - Alcoholism
KW - DSM-IV alcohol dependence
KW - Linkage
KW - Substance dependence
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U2 - 10.1016/j.drugalcdep.2010.07.017
DO - 10.1016/j.drugalcdep.2010.07.017
M3 - Article
C2 - 20817416
AN - SCOPUS:78651507402
SN - 0376-8716
VL - 113
SP - 125
EP - 132
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 2-3
ER -