A linkage study of bipolar illness

Wade H. Berrettini, Thomas N. Ferraro, Lynn R. Goldin, Sevilla D. Detera-Wadleigh, Henry Choi, David Muniec, Juliet J. Guroff, Diane M. Kazuba, John Nurnberger, Wang Ting Hsieh, Margret R. Hoehe, Elliot S. Gershon

Research output: Contribution to journalArticle

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Abstract

Background: Although genetic epidemiological studies of bipolar (BP) illness are consistent with a heritable component inherited risk factors remain unknown. The goal of the present study is to describe the localization of BP susceptibility loci through linkage strategies, including a genome- wide search. Methods: A linkage study of 22 BP families has been performed. These BP families include almost 400 persons, 173 of whom have been diagnosed as having BP I, schizoaffective, BP II with major depression, or recurrent unipolar illness. Using an autosomal dominant disease model with 85% or 50% age-dependent penetrance, and a recessive model with 85% penetrance, linkage analyses were performed assuming a narrow (BP and schizoaffective) or a broad (BP, schizoaffective, or unipolar) definition of the BP spectrum. Affected sibling pairs and affected pedigree member analyses were performed when positive lod scores were observed in multiple pedigrees. The present article describes linkage analysis of 310 DNA markers on chromosomes 1, 5p, 6, 8, 10q, 11q, and 12 to 18. Results: None of the loci examined disclosed compel ling evidence for linkage using lod score analyses. Model-independent analysis by multilocus affected pedigree member method in the pericentromeric chromosome 18 region disclosed statistically significant evidence (P<.0001) for a BP susceptibility gene in this region. Multilocus analysis by affected sibling pair method also disclosed evidence for linkage (P<.00008). Conclusions: Our results imply that a BP susceptibility gene exists near the centromere of chromosome 18. Confirmation of this finding (by independent investigators studying different pedigrees) has been published, suggesting that a valid BP disease linkage may have been discovered.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalArchives of General Psychiatry
Volume54
Issue number1
StatePublished - 1997

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Pedigree
Lod Score
Chromosomes, Human, Pair 18
Penetrance
Centromere
Chromosomes, Human, Pair 1
Genetic Markers
Genes
Epidemiologic Studies
Research Personnel
Genome

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Berrettini, W. H., Ferraro, T. N., Goldin, L. R., Detera-Wadleigh, S. D., Choi, H., Muniec, D., ... Gershon, E. S. (1997). A linkage study of bipolar illness. Archives of General Psychiatry, 54(1), 27-35.

A linkage study of bipolar illness. / Berrettini, Wade H.; Ferraro, Thomas N.; Goldin, Lynn R.; Detera-Wadleigh, Sevilla D.; Choi, Henry; Muniec, David; Guroff, Juliet J.; Kazuba, Diane M.; Nurnberger, John; Hsieh, Wang Ting; Hoehe, Margret R.; Gershon, Elliot S.

In: Archives of General Psychiatry, Vol. 54, No. 1, 1997, p. 27-35.

Research output: Contribution to journalArticle

Berrettini, WH, Ferraro, TN, Goldin, LR, Detera-Wadleigh, SD, Choi, H, Muniec, D, Guroff, JJ, Kazuba, DM, Nurnberger, J, Hsieh, WT, Hoehe, MR & Gershon, ES 1997, 'A linkage study of bipolar illness', Archives of General Psychiatry, vol. 54, no. 1, pp. 27-35.
Berrettini WH, Ferraro TN, Goldin LR, Detera-Wadleigh SD, Choi H, Muniec D et al. A linkage study of bipolar illness. Archives of General Psychiatry. 1997;54(1):27-35.
Berrettini, Wade H. ; Ferraro, Thomas N. ; Goldin, Lynn R. ; Detera-Wadleigh, Sevilla D. ; Choi, Henry ; Muniec, David ; Guroff, Juliet J. ; Kazuba, Diane M. ; Nurnberger, John ; Hsieh, Wang Ting ; Hoehe, Margret R. ; Gershon, Elliot S. / A linkage study of bipolar illness. In: Archives of General Psychiatry. 1997 ; Vol. 54, No. 1. pp. 27-35.
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AU - Goldin, Lynn R.

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AU - Choi, Henry

AU - Muniec, David

AU - Guroff, Juliet J.

AU - Kazuba, Diane M.

AU - Nurnberger, John

AU - Hsieh, Wang Ting

AU - Hoehe, Margret R.

AU - Gershon, Elliot S.

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N2 - Background: Although genetic epidemiological studies of bipolar (BP) illness are consistent with a heritable component inherited risk factors remain unknown. The goal of the present study is to describe the localization of BP susceptibility loci through linkage strategies, including a genome- wide search. Methods: A linkage study of 22 BP families has been performed. These BP families include almost 400 persons, 173 of whom have been diagnosed as having BP I, schizoaffective, BP II with major depression, or recurrent unipolar illness. Using an autosomal dominant disease model with 85% or 50% age-dependent penetrance, and a recessive model with 85% penetrance, linkage analyses were performed assuming a narrow (BP and schizoaffective) or a broad (BP, schizoaffective, or unipolar) definition of the BP spectrum. Affected sibling pairs and affected pedigree member analyses were performed when positive lod scores were observed in multiple pedigrees. The present article describes linkage analysis of 310 DNA markers on chromosomes 1, 5p, 6, 8, 10q, 11q, and 12 to 18. Results: None of the loci examined disclosed compel ling evidence for linkage using lod score analyses. Model-independent analysis by multilocus affected pedigree member method in the pericentromeric chromosome 18 region disclosed statistically significant evidence (P<.0001) for a BP susceptibility gene in this region. Multilocus analysis by affected sibling pair method also disclosed evidence for linkage (P<.00008). Conclusions: Our results imply that a BP susceptibility gene exists near the centromere of chromosome 18. Confirmation of this finding (by independent investigators studying different pedigrees) has been published, suggesting that a valid BP disease linkage may have been discovered.

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