Assessing the feasibility of linkage disequilibrium methods for mapping complex traits: An initial screen for bipolar disorder loci on chromosome 18

Linkage disequilibrium (LD) analysis:has been promoted as a method of mappi ng disease genes, particularly in isolated populations, but has not yet bee n used for genome-screening studies of complex disorders. We present result s of a study to investigate the feasibility of LD methods for genome:screen ing using a sample of individuals affected with severe bipolar mood disorde r (BP-I), from an isolated population of the Costa Rican central valley. Fo rty-eight patients with BP-I were genotyped for markers spaced at similar t o 6-cM intervals across chromosome 18. Chromosome 18 was chosen because a p revious genome-screening linkage study of two Costa Rican families had sugg ested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The re sults also support previously reported possible localizations (obtained fro m a separate collection of patients) of BP-I-susceptibility genes at two di stinct sites on this chromosome. Current limitations of LD screening for id entifying loci for complex traits are discussed, and recommendations are ma de for future research with these methods.