GENETIC ASSOCIATION STUDY IN PSYCHIATRY - ANALYTICAL EVALUATION AND A RECOMMENDATION

Recent analysis of the candidate gene, association study for psychiatric disorders have concluded that most statistically significant results are likely to be false positives because there are a large number of potential candidate loci and a low a priori probability that a given candidate locus will in fact be trait relevant. Hence, it was recommended that the alpha level (P level) be lowered for association studies. The present study demonstrates that lowering the alpha level to some fixed, predetermined value is not a recommended strategy, Rather, the probability of false positives (and false negatives) depends on such parameters as the prevalence of the disorder, the prevalence of the genotypes at the candidate locus, and the relative risk. In some areas of the parameter space, the adjustment to or may be modest. In other areas, however, even the requirement of one or more independent replications of the original results gives false positive rates exceeding 80% or 90%. Hence, the P levels required to minimize false positives may have to be changed from one statistical test to another even within the same study. A procedure for adjusting the probability level for a test of association between genotypes and a disorder is given. (C) 1994 Wiley-Liss, Inc.