Consortium; http://www.wtccc.org.uk/ccc2/projects/ccc2_pe.html) and one in the United States (the Consortium on the Genetics of Endophenotypes in Schizophrenia [32, 33]), have gathered cognitive, neuroanatomical and neurophysiological phenotypes that may act on the causal pathway to schizophrenia. The European consortium has so far published no genome-wide significant hits, while the United States consortium has reported linkage (not association) analyses of 12 endophenotypes, finding only one locus that exceeded genome-wide significance [34]. This result is no more successful than prior attempts to identify risk loci for schizophrenia through family-based linkage mapping [35, 36]. The authors point out: “while the biological basis of these endophenotypes may be simpler than that of schizophrenia per se, they nonetheless remain complex and appear to be highly polygenic. Conceivably, a refinement of these endophenotypes may probe a more specific physiology and thereby be sensitive to a more pure genetic signal” [34]. Is that optimistic conclusion realistic?
