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 al coholism genetics has had few findings that could be confirmed. Possib le sources for the largely negative results and suggested ways for imp roving the search for genes contributing to alcoholism risk are discus sed. These include the choice of phenotype to be studied, whether narr ow or broad, whether only mild or severe forms are included, and wheth er or not comorbidity should be excluded. The ascertainment schema for selecting families utilized in our laboratory which results in an esp ecially high recurrence risk will be discussed with respect to finding candidate genes. The complexity of the alcoholism phenotype will be d iscussed with respect to the existence of phenocopies, genetic heterog eneity, and the difficulties associated with defining the disorder in a way that covers all ages and both genders adequately. Finally, the e quivocal results found for the D-2 dopamine receptor are discussed wit h respect to current data analytic techniques, which emphasize affecte d sib-pairs, techniques that may be especially problematic for a disor der such as alcoholism that has marked tendencies for phenocopies to a rise. (C) 1998 Elsevier Science Inc.