McInnis et al. (2003a) conducted a genome-wide scan of 153 mostly Caucasian pedigrees as part of the NIMH Genetics Initiative for bipolar disorder. Markers were constructed by using CRIMAP (Lander and Green 1987), and GENEHUNTER-PLUS (Kong and Cox 1997) was used to compute nonparametric LOD scores. These investigators reported a suggestive LOD of 2.2 for the marker D10S1423 on chromosome 10p12 under an intermediate disease model. This linkage was also reported by Foroud et al. (2000) in the first 97 pedigrees from the genetics initiative. This region of 10p has been implicated in linkage studies of schizophrenia as well (Faraone et al. 1998; Schwab et al. 1998).
Linkage to 10q has been reported by several groups, including Ewald et al. (1999) and Cichon et al. (2001). Using multipoint parametric analysis, Liu et al. (2003) obtained a suggestive LOD of 2.33 at 10q24 under a dominant, narrowly defined phenotype. However, a follow-up ASP analysis found a maximum LOD score of only 1.57 for this region. In their weighted meta-analysis, under a narrowly defined model, Segurado et al. (2003) found evidence that the region 10q11.21-q22.1 may contain genes with weak effects on bipolar disorder.
Toward clarifying the relationship between this region and bipolar disorder and schizophrenia, Ewald et al. (2002a) examined allelic association and chromosome segment and haplotype sharing on chromosome 10q26 in a sample of distantly related patients with schizophrenia or bipolar disorder and controls. In an isolated population sample on the Faroe Islands, patient lineages were traced back to determine familial relationships. Twenty-two microsatellite markers were used, and both assumption-free tests and tests based upon genealogical relation ships were used. Allele frequency and haplotype segments were compared between patients and controls by using CLUMP (Sham and Curtis 1995). Comparing the combined patient group to the controls revealed an allelic association at marker D10S1723, which is consistent with the notion of a common susceptibility region for the two disorders. Another region between D10S214 and D10S505 showed evidence for increased haplotype sharing in bipolar disorder.
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