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 Leon; Lodewijk A. Sandkuijl; Nelson B. Freimer

doi:10.1086/302400

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

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

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 language	English (US)
Pages (from-to)	1670-1678
Number of pages	9
Journal	American Journal of Human Genetics
Volume	64
Issue number	6
DOIs	https://doi.org/10.1086/302400
State	Published - 1999

Bibliographical note

Funding 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.

Publisher link

10.1086/302400

Find It

Find It at U of M Libraries

Cite this

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

Escamilla, MA, McInnes, LA, Spesny, M, Reus, VI, Service, SK, Shimayoshi, N, Tyler, DJ, Silva, S, Molina, J, Gallegos, A, Meza, L, Cruz, ML, Batki, S, Vinogradov, S, Neylan, T, Nguyen, JB, Fournier, E, Araya, C, Barondes, SH, Leon, P, Sandkuijl, LA & Freimer, NB 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, vol. 64, no. 6, pp. 1670-1678. https://doi.org/10.1086/302400

@article{0b70546e86b447a98c4bb2c5b40c59b8,

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

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.",

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

note = "Funding 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. ",

year = "1999",

doi = "10.1086/302400",

language = "English (US)",

volume = "64",

pages = "1670--1678",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Assessing the feasibility of linkage disequilibrium methods for mapping complex traits

T2 - An initial screen for bipolar disorder loci on chromosome 18

AU - Escamilla, Michael A.

AU - McInnes, L. Alison

AU - Spesny, Mitzi

AU - Reus, Victor I.

AU - Service, Susan K.

AU - Shimayoshi, Norito

AU - Tyler, David J.

AU - Silva, Sandra

AU - Molina, Julio

AU - Gallegos, Alvaro

AU - Meza, Luis

AU - Cruz, Maria L.

AU - Batki, Steven

AU - Vinogradov, Sophia

AU - Neylan, Thomas

AU - Nguyen, Jasmine B.

AU - Fournier, Eduardo

AU - Araya, Carmen

AU - Barondes, Samuel H.

AU - Leon, Pedro

AU - Sandkuijl, Lodewijk A.

AU - Freimer, Nelson B.

N1 - Funding 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.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0003407869&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0003407869&partnerID=8YFLogxK

U2 - 10.1086/302400

DO - 10.1086/302400

M3 - Article

C2 - 10330354

AN - SCOPUS:0003407869

SN - 0002-9297

VL - 64

SP - 1670

EP - 1678

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

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

Abstract

Bibliographical note

Publisher link

Find It

Other files and links

Fingerprint

Cite this