Continuing the search for a predisposition gene for affective disorder in the Old Order Amish: Linkage analysis of 150 markers

Four pedigrees of the Old Order Amish were used for linkage analysis of over 150 polymorphic genetic markers. The pedigrees contain a total of 162 members of whom 125 were genotyped. Three diagnostic schemes were used resulting in 23, 32, and 40 affected individuals, respectively. Analyses were conducted assuming an autosomal dominant mode of inheritance with an age-dependent penetrance (maximum penetrance = 0.5). The genetic model parameters were consistent with those obtained from segregation analysis. Although none of the markers showed significant linkage, these pedigrees have excellent power to detect linkage (91% of lod scores from simulated data exceeded 3.0, for a 4-allele marker) and adequate power to detect linkage if there is more than 1 locus segregating in this population (71% of lod scores from simulated data exceeded 3.0 under 15% heterogeneity). Linkage was excluded from approximately 60% of the markers tested (at {theta} = 0.01). Sensitivity analyses were conducted to detect changes in lod scores with individual changes in diagnostic status.