Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BPI), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at ~6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested 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 results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I-susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health grants MH00916, MH49499, MH48695, and MH47563; the National Alliance for Research on Schizophrenia and DepressionYoung Investigator Awards (to M.A.E. and N.B.F.); the American Psychiatric Association's Program for Minority Research Training in Psychiatry Award (to M.A.E.); and the Veterans Administration Research Psychiatrist Award (to L.A.M.). We thank Lauren Smith for assistance in collating the best estimate materials. M.A.E. thanks Dr. Carlos Martinez for his support and suggestions regarding this research work. Above all we would like to thank the patients and family members who participated in this project and the Costa Rica institutions that made this work possible, including the Hospital Nacional Psiquiatrico, The Hospital Calderon Guardia, The Ministry of Science, and the Caja Costarricense de Seguro Social.