The discovery of expanding microsatellite repeat mechanisms for a variety of diseases has spurred renewed interest in testing for genetic anticipation in complex diseases. However, standard statistical methods can be shown to be inappropriate for this purpose. We derive a new statistical test for co
A new test statistic for linkage applied to bipolar disorder and marker D18S41
โ Scribed by M.A. Cleves; D.V. Dawson; R.C. Elston; A.H. Schnell
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 50 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0741-0395
No coin nor oath required. For personal study only.
โฆ Synopsis
We applied a new test statistic for linkage that removes the traditional assumption of equal female (2 ) and male (2 ) recombination fractions by testing H :
reported possible linkage between a suggested susceptibility locus for bipolar affective disorder and marker D18S41 on chromosome 18 [Stine et al., 1995]. We used penetrance functions fitting the description of those used by Stine et al.
[1995] assuming a continuous age-dependent logistic distribution. Maximum likelihood marker allele frequencies were estimated assuming Hardy-Weinberg equilibrium. Results from the traditional lod-score analyses do not strongly support the existence of linkage between the disease locus and marker D18S41.
Similarly, the new test statistic for linkage failed to provide evidence in support of linkage. This was true whether dominant or recessive models of inheritance were assumed, and whether the analyses included all available pedigrees or were confined to paternally transmitted pedigrees. The appreciable difference found between our lod scores and those obtained by Stine et al. [1995] can be attributed to differences in the assumptions made regarding the age-dependent penetrance function, the marker allele frequencies, or both.
๐ SIMILAR VOLUMES
Despite the evidence that major gene effects exist for bipolar disorder (BP), efforts to map BP loci have so far been unsuccessful. A strategy for mapping BP loci is described, focused on investigation of large pedigrees from a genetically homogenous population, that of Costa Rica. This approach is
Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, s
Since its introduction into the statistical genetics literature, the transmission disequilibrium test (TDT) has seen widespread use in analyses of linkage and association due not only to its simplicity but also to its desirable properties relative to other within-family analytic methods. In this pap