Alternative phenotypes for the complex genetics of schizophrenia

The complexity of the genetics of schizophrenia has been described by many investigators. In the absence of simple Mendelian inheritance, genetic link age has not achieved the definitive results found in other illnesses, where such methods have led to the identification of responsible genes. Alternat ive phenotypes for linkage analysis are proposed as one solution to this pr oblem. These phenotypes, representative of discrete biological deficits in schizophrenia, may more closely reflect the effect of a single gene than th e illness itself The Mendelian inheritance of one alternative phenotype, fa ilure to inhibit the P50 auditory evoked response to repeated stimuli, has resulted in successful linkage of the deficit to the locus of a candidate g ene, the alpha 7-nicotinic acetylcholine receptor on chromosome 15q14. Furt her support for this linkage has recently been found in families from the N IMH Schizophrenia Genetics Initiative, using schizophrenia as the phenotype . Alternative phenotypes based on discrete biological deficits in schizophr enia have enhanced power for linkage analysis. Such analyses can not only f acilitate understanding of the genetic transmission of schizophrenia, but t hey also provide further support for neurobiological characterizations of t he pathophysiology of schizophrenia; however, identification of responsible genetic mutations is necessary before definitive conclusions can be reache d. Biol Psychiatry 1999;45: 551-558 (C) 1999 Society of Biological Psychiat ry.