Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study

Ian R. Gizer, Cindy L. Ehlers, Cassandra Vieten, Kimberly L. Seaton-Smith, Heidi Feiler, James V. Lee, Samantha K. Segall, David A. Gilder, Kirk C. Wilhelmsen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalDrug and Alcohol Dependence
Volume113
Issue number2-3
DOIs
StatePublished - Jan 15 2011
Externally publishedYes

Fingerprint

Alcoholism
Alcohols
Chromosomes
Genes
Diagnostic and Statistical Manual of Mental Disorders
Drinking
Cluster Analysis
Medical problems
Genome
Phenotype
Health

Keywords

  • Addiction
  • Alcoholism
  • DSM-IV alcohol dependence
  • Linkage
  • Substance dependence

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Toxicology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Gizer, I. R., Ehlers, C. L., Vieten, C., Seaton-Smith, K. L., Feiler, H., Lee, J. V., ... Wilhelmsen, K. C. (2011). Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study. Drug and Alcohol Dependence, 113(2-3), 125-132. https://doi.org/10.1016/j.drugalcdep.2010.07.017

Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study. / Gizer, Ian R.; Ehlers, Cindy L.; Vieten, Cassandra; Seaton-Smith, Kimberly L.; Feiler, Heidi; Lee, James V.; Segall, Samantha K.; Gilder, David A.; Wilhelmsen, Kirk C.

In: Drug and Alcohol Dependence, Vol. 113, No. 2-3, 15.01.2011, p. 125-132.

Research output: Contribution to journalArticle

Gizer, IR, Ehlers, CL, Vieten, C, Seaton-Smith, KL, Feiler, H, Lee, JV, Segall, SK, Gilder, DA & Wilhelmsen, KC 2011, 'Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study', Drug and Alcohol Dependence, vol. 113, no. 2-3, pp. 125-132. https://doi.org/10.1016/j.drugalcdep.2010.07.017
Gizer, Ian R. ; Ehlers, Cindy L. ; Vieten, Cassandra ; Seaton-Smith, Kimberly L. ; Feiler, Heidi ; Lee, James V. ; Segall, Samantha K. ; Gilder, David A. ; Wilhelmsen, Kirk C. / Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study. In: Drug and Alcohol Dependence. 2011 ; Vol. 113, No. 2-3. pp. 125-132.
@article{e309f66fbb854b82af6a26051e9ee2a2,
title = "Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study",
abstract = "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.",
keywords = "Addiction, Alcoholism, DSM-IV alcohol dependence, Linkage, Substance dependence",
author = "Gizer, {Ian R.} and Ehlers, {Cindy L.} and Cassandra Vieten and Seaton-Smith, {Kimberly L.} and Heidi Feiler and Lee, {James V.} and Segall, {Samantha K.} and Gilder, {David A.} and Wilhelmsen, {Kirk C.}",
year = "2011",
month = "1",
day = "15",
doi = "10.1016/j.drugalcdep.2010.07.017",
language = "English (US)",
volume = "113",
pages = "125--132",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
publisher = "Elsevier Ireland Ltd",
number = "2-3",

}

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

AU - Lee, James V.

AU - Segall, Samantha K.

AU - Gilder, David A.

AU - Wilhelmsen, Kirk C.

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

UR - http://www.scopus.com/inward/record.url?scp=78651507402&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651507402&partnerID=8YFLogxK

U2 - 10.1016/j.drugalcdep.2010.07.017

DO - 10.1016/j.drugalcdep.2010.07.017

M3 - Article

C2 - 20817416

AN - SCOPUS:78651507402

VL - 113

SP - 125

EP - 132

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

SN - 0376-8716

IS - 2-3

ER -