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.
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.
Authors: Vivia V McCutcheon; Arpana Agrawal; Andrew C Heath; Howard J Edenberg; Victor M Hesselbrock; Marc A Schuckit; John R Kramer; Kathleen K Bucholz Journal: Alcohol Clin Exp Res Date: 2011-06-01 Impact factor: 3.455
Authors: John P Rice; Sarah M Hartz; Arpana Agrawal; Laura Almasy; Siiri Bennett; Naomi Breslau; Kathleen K Bucholz; Kimberly F Doheny; Howard J Edenberg; Alison M Goate; Victor Hesselbrock; William B Howells; Eric O Johnson; John Kramer; Robert F Krueger; Samuel Kuperman; Cathy Laurie; Teri A Manolio; Rosalind J Neuman; John I Nurnberger; Bernice Porjesz; Elizabeth Pugh; Erin M Ramos; Nancy Saccone; Scott Saccone; Marc Schuckit; Laura J Bierut Journal: Addiction Date: 2012-06-15 Impact factor: 6.526
Authors: Mark Zlojutro; Niklas Manz; Madhavi Rangaswamy; Xiaoling Xuei; Leah Flury-Wetherill; Daniel Koller; Laura J Bierut; Alison Goate; Victor Hesselbrock; Samuel Kuperman; John Nurnberger; John P Rice; Marc A Schuckit; Tatiana Foroud; Howard J Edenberg; Bernice Porjesz; Laura Almasy Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2010-11-02 Impact factor: 3.568
Authors: Chella Kamarajan; Ashwini K Pandey; David B Chorlian; Niklas Manz; Arthur T Stimus; Lance O Bauer; Victor M Hesselbrock; Marc A Schuckit; Samuel Kuperman; John Kramer; Bernice Porjesz Journal: Int J Psychophysiol Date: 2015-09-18 Impact factor: 2.997
Authors: Alexander A Bachmanov; Danielle R Reed; Xia Li; Shanru Li; Gary K Beauchamp; Michael G Tordoff Journal: Genome Res Date: 2002-08 Impact factor: 9.043
Authors: Saurabh Ghosh; Laura J Bierut; Bernice Porjesz; Howard J Edenberg; Danielle Dick; Alison Goate; Victor Hesselbrock; John Nurnberger; Tatiana Foroud; John Kramer; John Rice; Henri Begleiter Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2008-10-05 Impact factor: 3.568