Linkage of an Alcoholism-Related Severity Phenotype to Chromosome 16

Alcohol Clin Exp Res. 1998 Dec;22(9):2035-42.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alcohol Withdrawal Delirium / genetics
  • Alcohol Withdrawal Delirium / rehabilitation
  • Alcoholism / genetics*
  • Alcoholism / rehabilitation
  • Alleles
  • Chromosomes, Human, Pair 16*
  • Female
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Models, Genetic
  • Phenotype*

Substances

  • Genetic Markers