title: Linkage of an alcoholism-related severity phenotype to chromosome 16.
abstract: There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.
authors.affiliation: Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: K K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: R J
authors.initials: RJ
authors.lastname: Neuman
authors.forename: B
authors.initials: B
authors.lastname: Porjesz
authors.forename: D L
authors.initials: DL
authors.lastname: Koller
authors.forename: J
authors.initials: J
authors.lastname: Rice
authors.forename: T
authors.initials: T
authors.lastname: Reich
authors.forename: L J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: C R
authors.initials: CR
authors.lastname: Cloninger
authors.forename: J I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: T K
authors.initials: TK
authors.lastname: Li
authors.forename: P M
authors.initials: PM
authors.lastname: Conneally
authors.forename: J A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: R
authors.initials: R
authors.lastname: Crowe
authors.forename: V
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: M
authors.initials: M
authors.lastname: Schuckit
authors.forename: H
authors.initials: H
authors.lastname: Begleiter
mesh_terms: D000328:Adult; D000430:Alcohol Withdrawal Delirium / Q000235:genetics / Q000534:rehabilitation; D000437:Alcoholism / Q000235:genetics* / Q000534:rehabilitation; D000483:Alleles; D002885:Chromosomes, Human, Pair 16; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010641:Phenotype
chemical_list: D005819:Genetic Markers