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

Michael A. Escamilla, L. Alison McInnes, Mitzi Spesny, Victor I. Reus, Susan K. Service, Norito Shimayoshi, David J. Tyler, Sandra Silva, Julio Molina, Alvaro Gallegos, Luis Meza, Maria L. Cruz, Steven Batki, Sophia Vinogradov, Thomas Neylan, Jasmine B. Nguyen, Eduardo Fournier, Carmen Araya, Samuel H. Barondes, Pedro LeonLodewijk A. Sandkuijl, Nelson B. Freimer

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1670-1678
Number of pages9
JournalAmerican Journal of Human Genetics
Volume64
Issue number6
DOIs
StatePublished - 1999

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    Escamilla, M. A., McInnes, L. A., Spesny, M., Reus, V. I., Service, S. K., Shimayoshi, N., Tyler, D. J., Silva, S., Molina, J., Gallegos, A., Meza, L., Cruz, M. L., Batki, S., Vinogradov, S., Neylan, T., Nguyen, J. B., Fournier, E., Araya, C., Barondes, S. H., ... Freimer, N. B. (1999). Assessing the feasibility of linkage disequilibrium methods for mapping complex traits: An initial screen for bipolar disorder loci on chromosome 18. American Journal of Human Genetics, 64(6), 1670-1678. https://doi.org/10.1086/302400