Linkage of an alcoholism-related severity phenotype to chromosome 16.
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.
Foroud
T
T
Indiana University School of Medicine, Indianapolis 46202, USA.
Bucholz
K K
KK
Edenberg
H J
HJ
Goate
A
A
Neuman
R J
RJ
Porjesz
B
B
Koller
D L
DL
Rice
J
J
Reich
T
T
Bierut
L J
LJ
Cloninger
C R
CR
Nurnberger
J I
JI
Li
T K
TK
Conneally
P M
PM
Tischfield
J A
JA
Crowe
R
R
Hesselbrock
V
V
Schuckit
M
M
Begleiter
H
H
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
D005819:Genetic Markers