Alcoholism susceptibility loci: Confirmation studies in a replicate sample and further mapping

Tatiana Foroud, Howard Edenberg, Alison Goate, John Rice, Leah Flury, Daniel L. Koller, Laura J. Bierut, P. Michael Conneally, John Nurnberger, Kathleen K. Bucholz, Ting Kai Li, Victor Hesselbrock, Raymond Crowe, Marc Schuckit, Bernice Porjesz, Henri Begleiter, Theodore Reich

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Background: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. Methods: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. Results: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). Conclusions: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets.

Original languageEnglish
Pages (from-to)933-945
Number of pages13
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number7
StatePublished - Jul 2000

Fingerprint

Chromosomes
Alcoholism
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 7
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 3
Alcoholics
Genetic Loci
International Classification of Diseases
Genetic Predisposition to Disease
Diagnostic and Statistical Manual of Mental Disorders
Datasets
Siblings
Alcohols

Keywords

  • Alcoholism
  • Nonparametric Linkage Analysis
  • Sibling Pair
  • Susceptibility Genes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Alcoholism susceptibility loci : Confirmation studies in a replicate sample and further mapping. / Foroud, Tatiana; Edenberg, Howard; Goate, Alison; Rice, John; Flury, Leah; Koller, Daniel L.; Bierut, Laura J.; Conneally, P. Michael; Nurnberger, John; Bucholz, Kathleen K.; Li, Ting Kai; Hesselbrock, Victor; Crowe, Raymond; Schuckit, Marc; Porjesz, Bernice; Begleiter, Henri; Reich, Theodore.

In: Alcoholism: Clinical and Experimental Research, Vol. 24, No. 7, 07.2000, p. 933-945.

Research output: Contribution to journalArticle

Foroud, T, Edenberg, H, Goate, A, Rice, J, Flury, L, Koller, DL, Bierut, LJ, Conneally, PM, Nurnberger, J, Bucholz, KK, Li, TK, Hesselbrock, V, Crowe, R, Schuckit, M, Porjesz, B, Begleiter, H & Reich, T 2000, 'Alcoholism susceptibility loci: Confirmation studies in a replicate sample and further mapping', Alcoholism: Clinical and Experimental Research, vol. 24, no. 7, pp. 933-945.
Foroud, Tatiana ; Edenberg, Howard ; Goate, Alison ; Rice, John ; Flury, Leah ; Koller, Daniel L. ; Bierut, Laura J. ; Conneally, P. Michael ; Nurnberger, John ; Bucholz, Kathleen K. ; Li, Ting Kai ; Hesselbrock, Victor ; Crowe, Raymond ; Schuckit, Marc ; Porjesz, Bernice ; Begleiter, Henri ; Reich, Theodore. / Alcoholism susceptibility loci : Confirmation studies in a replicate sample and further mapping. In: Alcoholism: Clinical and Experimental Research. 2000 ; Vol. 24, No. 7. pp. 933-945.
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abstract = "Background: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. Methods: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. Results: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). Conclusions: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets.",
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AU - Edenberg, Howard

AU - Goate, Alison

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AU - Flury, Leah

AU - Koller, Daniel L.

AU - Bierut, Laura J.

AU - Conneally, P. Michael

AU - Nurnberger, John

AU - Bucholz, Kathleen K.

AU - Li, Ting Kai

AU - Hesselbrock, Victor

AU - Crowe, Raymond

AU - Schuckit, Marc

AU - Porjesz, Bernice

AU - Begleiter, Henri

AU - Reich, Theodore

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N2 - Background: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. Methods: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. Results: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). Conclusions: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets.

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