| This thesis discusses some of the problems encountered when trying to identify genes that underlie the liability to develop complex traits, especially psychiatric disorders. In chapter I, a linkage analysis between chromosome 5 markers an schizophrenia is used to present the problems of applying the lod score method to traits with unknown mode of inheritance. The dependence of lod scores on transmission parameters and phenotypic changes is shown. Multipoint lod scores are found to be very sensitive to misspecifications of the transmission parameters and recommendations to improve the robustness of multipoint lod scores are given. In chapter II, a linkage analysis between chromosome 21 markers and early-onset Alzheimer's disease shows the power of using a subset of families showing a Mendelian pattern of transmission of a trait that otherwise does not exhibit simple Mendelian patterns. The limitations of pooling several small families in a linkage analysis are discussed. The segregation of chromosome 21 in one large pedigree signalled the region containing the amyloid precursor protein gene as carrying the disease mutation. In chapter III, an analysis of the cohort effect of Major Depressive Disorder (MDD) suggests that this effect could be at least partly due to impaired recall of MDD episodes. In addition, a trend towards a decreased familiality of MDD among younger cohorts is found. The implications of these findings for a linkage analysis of MDD are presented. In chapter IV, an analysis of Na... |
