94-97 TABLE II. Linkage results (P values) for bipolar disorder and 18p11 DNA markers. *MP = multipoint; †NR = not reported; ‡NS= not significant; §results for paternal kindreds; Ilschizophrenia probands. Wildenauer et al98,99 studied

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for schizoaffective and UP disorders Inhibitors,research,lifescience,medical are found among die first-degree relatives of BP probands, compared to firstdegree relatives of controls.20,24,29 Further, Kendler et al101 found increased risk for schizophrenia among the relatives of individuals with psychotic affective illness. Table II summarizes nominal significance Inhibitors,research,lifescience,medical levels for statistical analysis of marker

genotypes located in a ≈ 10-cM region of chromosome 18p11. Results are presented for a narrow phenotypic definition in which only BPI was affected96,97 or for a broader definition.93,94,102 If the locus described by Berrettini Inhibitors,research,lifescience,medical et al92,93 increases risk for BP disorder by a factor of ≈2, simulations indicate that ≈200 affected sibling pairs are required to have >90% power to detect it103 at a significance level (LOD >1.2 or P<0.01) adequate for confirmation.36 Various authors104-110 have studied samples from European, Icelandic, and North American populations, and found no evidence for confirmation Astemizole of linkage on 18p, but these sample sizes did not exceed 100 affected sibling pairs in any one study. However, the 18p BP locus has not been confirmed in the National Institutes of Mental Health (NIMH) Collaborative Study111 in which an adequate sample size was evaluated. Genetic Analysis Workshop 10112 allowed statistical geneticists to analyze data from Berrettini et al,93 Nothen et al,96 Stinc et al,94 Knowlcs et al,97 and Kalsi et al.104 Results of several different analyses were consistent with the existence of a BP susceptibility gene. For example, Lin and Bale113 analyzed the entire data set of 382 affected sibling pairs (defined under a broad affection status model) using a multipoint nonparametric method.