Linkage studies of bipolar disorder with chromosome 18 markers

Abstract

Evidence consistent with the existence of genetic linkage between bipolar disorder and three regions on chromosome 18, the pericentromeric region, 18q21, and 18q22-q23 have been reported. Some analyses indicated greater evidence for linkage in pedigrees in which paternal transmission of disease occurs. We have undertaken linkage analyses using 12 highly polymorphic markers spanning these three regions of interest in a sample of 48 U.K. bipolar pedigrees. The sample comprises predominantly nuclear families and includes 118 subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM IV) bipolar I disorder and 147 subjects with broadly defined phenotype. Our data do not provide support for linkage using either parametric or nonparametric analyses. Evidence for linkage was not significantly increased by analyses that allowed for heterogeneity nor by analysing the subset of pedigrees consistent with paternal transmission.

The Wellcome trust UK–Irish bipolar affective disorder sibling-pair genome screen: first stage report

“…42 There have of course been studies providing less clear support for some of these findings, [70][71][72] and indeed others which have failed to find any evidence at all of linkage to chromosome 18. [73][74][75][76][77] Nevertheless, chromosome 18 remains very interesting, and could well be one of the first chromosomes to yield a susceptibility gene for a major psychiatric disorder.…”

Association between polymorphisms in the metallophosphoesterase (MPPE1) gene and bipolar disorder

“…Family, adoption and twin studies show that BPD has a strong genetic component (Craddock and Jones 1999). Linkage studies in BPD suggest that a susceptibility locus exists on chromosome 18p11 (Bennett and others 2002; Berrettini and others 1994; Bowen and others 1999; Detera-Wadleigh and others 1999; McInnes and others 1996; Mukherjee and others 2006; Nothen and others 1999; Stine and others 1995). Several genes in that region have been investigated previously but results are inconclusive and no functional variations of major effect have been identified so far (Berrettini and others 1998; Chavarria-Siles and others 2007; Corradi and others 2005; Esterling and others 1997; Evans and others 2008; Ishiguro and others 2001; Lohoff and Berrettini 2005; Lohoff and others 2008a; Lohoff and others 2008b; Mulle and others 2007; Ohnishi and others 2007; Reyes and others 2002; Rojas and others 2000; Tsiouris and others 1996; Washizuka and others 2004; Washizuka and others 2003; Weller and others 2006; Yoshikawa and others 2000; Yoshikawa and others 1997).…”