Alternative strategies for uncovering genes contributing to alcoholism risk: unpredictable findings in a genetic wonderland.
In spite of technological advances in genetic mapping, the field of alcoholism genetics has had few findings that could be confirmed. Possible sources for the largely negative results and suggested ways for improving the search for genes contributing to alcoholism risk are discussed. These include the choice of phenotype to be studied, whether narrow or broad, whether only mild or severe forms are included, and whether or not comorbidity should be excluded. The ascertainment schema for selecting families utilized in our laboratory which results in an especially high recurrence risk will be discussed with respect to finding candidate genes. The complexity of the alcoholism phenotype will be discussed with respect to the existence of phenocopies, genetic heterogeneity, and the difficulties associated with defining the disorder in a way that covers all ages and both genders adequately. Finally, the equivocal results found for the D2 dopamine receptor are discussed with respect to current data analytic techniques, which emphasize affected sib-pairs, techniques that may be especially problematic for a disorder such as alcoholism that has marked tendencies for phenocopies to arise.
Hill
S Y
SY
University of Pittsburgh Medical Center, Department of Psychiatry, PA 15213, USA.
D000437:Alcoholism / Q000235:genetics*; D001519:Behavior / Q000502:physiology; D005821:Genetic Techniques; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors