33 (95% confidence interval [CI] 1.04-1.70, P=0.02) (Figure 2).

Meta-analyses are less sensitive to stratification and admixture (unless these are present in the samples included in the meta-analysis), since original data are not pooled and the unit, of analysis is studies and not individuals. Figure 2. Meta-analysis of DRD3 risk RAAS inhibitor ic50 allele (gly) among seven of the groups included in the pooled analysis reported by Lerer et al6 (the African-American group was excluded because of skewed distribution) and three other published studies.7-9 The size of each … Inhibitors,research,lifescience,medical The findings of our studies of the DRD3 ser9gly polymorphism and TD indicate that, when pooled pharmacogenetic analyses arc conducted on well-characterized samples, Inhibitors,research,lifescience,medical it is possible to control for the potentially artifactual effects of ethnicity. This is important, because it is essential to gather large samples for pharmacogenetic studies so as to have sufficient statistical power. The same general strategy was implemented to examine the association of the serotonin 5-HT2A receptor gene and TD,10 and also to examine association of the 5-HT2C receptor gene with unipolar and bipolar affective disorder.11 When using ostensibly homogeneous Inhibitors,research,lifescience,medical samples, the genomic control method may be implemented to rule out population

influences on the markers being studied.12 This involves genotyping additional markers that are putatively unrelated to the phenotype, and these are used to determine the degree of stratification that is present in the sample. Demography matters: age-related Inhibitors,research,lifescience,medical effects of genetic variants It is often not taken into account, that genetic variants may have differing functional importance depending on the stage of the life cycle. This is obvious in the case of genes that predispose to disorders of later life such as Alzheimer’s disease (although the pathophysiological effects of variations in these genes may be Inhibitors,research,lifescience,medical manifested long before the clinical threshold is crossed). Similarly, genes that, influence neurodevelopment in utero may be associated with susceptibility to schizophrenia that only becomes clinically manifest, in late adolescence.

Agerelatedness may also be important, in pharmacogenetic phenotypes. We have observed an age-related association of two serotonergic genes, the 5-HT2C (HTR2C) and the 5-HT2A receptor (HTR2A) with susceptibility to TD.13 Our finding with the 5-HT2A receptor has been replicated in a large multicenter study.10 In an earlier report13 (Figure Dipeptidyl peptidase 3), we showed that scores on the Abnormal Involuntary Movements Scale (AIMS, the hallmark of TD) were significantly related to the ser23 allele of the cys23ser polymorphism of the 5-HTC receptor gene and to the 102C allele of the T102C polymorphism in the 5-HT2A receptor gene, in older but, not, younger patients. We sought, to replicate this finding the context of a multicenter study involving 635 patients, 256 of whom manifested TD and 379 of whom did not.