Occam’s Razor Cuts Deep

I have in front of me an April 2008 editorial in the American Journal of Psychiatry regarding the failure of Sanders, et al. to validate any of 14 “candidate genes” for schizophrenia. The editorial says it all: ” The simplest explanation is that for the broadly recruited cases and comparison subjects used in this study, common DNA variation in these genes is just not correlated with the schizophrenia phenotype, as defined by the investigators.”Several highly respected European and American researchers examined the relationship of  variants of 14 genes suspected of causing schizophrenia and found no significant relationship between the presence of these variants and the presence of schizophrenia or of presumably related disorders. The editorial, while not denying the results, attempts to explain them in a way that is consistent with maintaining the “known” genetic cause of schizophrenia.

The various approaches outlined in the editorial serve only to underline the problem. Applying the criterion known in science as Occam’s Razor, if the statistical power of studies with literally thousands of subjects is insufficient to detect an effect, the simplest (and best) explanation is that the effect is not there. The suggestion in the editorial that studies with more power are needed merely emphasizes the weakness of the sought-for effect–and is not exactly great science. The suggestion I have seen elsewhere that perhaps scores of genes, each with a nearly undetectable effect, are responsible for schizophrenia is incoherent. (Indeed, it should be in the dictionary next to the definition of “hand-waving.”)

I never cease to be amazed at an aspect of  research on the genetics of schizophrenia that pops up again and again: There is a profound unwillingness to accept what the numbers say when they do not yield the “right” answer, which would be that there are well-defined genetic markers for schizophrenia. One occasionally sees this rejection of the results leading researchers who do not understand the logic of statistics and research design to draw positive conclusions from negative results. I suppose that researchers in this domain, secure in the knowledge that schizophrenia is a genetic disorder, assumed that it was simply a matter of time before technology aided in the discovery of the gene or genes responsible. When will they decide to reevaluate the logic that led them to this point, and accept the possibility that the vaunted results of twin studies are misleading because of conceptual flaws or methodological flaws or both?