So far, negative linkage results have been obtained with the DBH gene.35 Chromosome 13. The region 13q codes for the

serotonin receptor 5-HT2A gene, which has been reported to be associated with schizophrenia.36 Positive lod scores have been obtained with independent samples from Europe, Asia, Africa, USA, or Canada. Chromosome 15. The first evidence for a possible implication of chromosome Inhibitors,research,lifescience,medical 15 was the report #MLN8237 randurls[1|1|,|CHEM1|]# of linkage with P50 sensory gating deficit in the region 15q13-q14.37 A positive lod score was obtained with the gene encoding the α7 nicotinic cholinergic receptor subunit (CHRNA7) when using the sensory gating phenotype; the lod score dropped when using schizophrenia as the phenotype. With polymorphic markers located in the same regions, positive results have been obtained by several groups, while two studies failed to find any evidence for involvement of this region.38,39 Chromosome 18. Interest in chromosome 18 began with the report of positive linkage with bipolar disorder.40 Positive results, not always replicated, have mostly Inhibitors,research,lifescience,medical been obtained when including both affective disorders and schizophrenia as the affected phenotype.41 Positive results have been obtained with the gene encoding for the subunit of the olfactory G-protein (GOLF). Inhibitors,research,lifescience,medical Chromosome 22. Discrepant results have been obtained with markers spanning chromosome 22, which is also known to be associated with velocardiofacial syndrome (VCFS). Thirty percent of patients presenting

with this syndrome carry a diagnosis of schizophrenia.42 Inhibitors,research,lifescience,medical The gene encoding for catechol-O-methyl transferase (COMT) is located in the region 22q11 and has been suggested to be involved with the psychotic symptoms observed in VCFS.43 X chromosome. The X chromosome was initially suggested to be a Inhibitors,research,lifescience,medical chromosome of interest due to the well-known gender differences in schizophrenia. A pseudoautosomal locus that would account for those differences was suggested by Crow et al.44 Discrepant results were obtained thereafter. Results have already been published in the field of schizophrenia pharmacogenetics.

In particular, an association has been reported between the D4 receptor gene and good response to clozapine,45 while nonresponders to clozapine demonstrated associations with particular alleles of the 5-HT2A receptor gene.46 These findings have not always Non-specific serine/threonine protein kinase been replicated, dampening enthusiasm. Altogether, all these results may appear confusing. The clinical heterogeneity of the illness is one of several explanations for these discrepancies. The use of linkage analysis methods in comparison with nonparametric methods (which do not apply any assumptions on the mode of inheritance) has been thoroughly discussed. The value of performing association studies testing the implication of candidate genes is clear. However, Riley and McGuffin18 have emphasized that larger clinical samples than originally anticipated will be needed both for studies in multiply affected families and for sporadic cases.