A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2

Sevilla D. Detera-Wadleigh, Judith A. Badner, Wade H. Berrettini, Takeo Yoshikawa, Lynn R. Goldin, Gordon Turner, Denise Y. Rollins, Tracy Moses, Alan R. Sanders, Jayaprakash D. Karkera, Lisa E. Esterling, Jin Zeng, Thomas N. Ferraro, Juliet J. Guroff, Diane Kazuba, Mary E. Maxwell, John Nurnberger, Elliot S. Gershon

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Abstract

Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on ≃396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0.000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder. Suggestive linkage was found on 1q31-q32 (lod = 2.67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054). Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0.00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.

Original languageEnglish
Pages (from-to)5604-5609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number10
DOIs
StatePublished - May 11 1999

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Bipolar Disorder
Genome
Schizophrenia
Depression
Gene Components
Twin Studies
Pedigree
Psychotic Disorders
Microsatellite Repeats
Phenotype

ASJC Scopus subject areas

  • Genetics
  • General

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A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2. / Detera-Wadleigh, Sevilla D.; Badner, Judith A.; Berrettini, Wade H.; Yoshikawa, Takeo; Goldin, Lynn R.; Turner, Gordon; Rollins, Denise Y.; Moses, Tracy; Sanders, Alan R.; Karkera, Jayaprakash D.; Esterling, Lisa E.; Zeng, Jin; Ferraro, Thomas N.; Guroff, Juliet J.; Kazuba, Diane; Maxwell, Mary E.; Nurnberger, John; Gershon, Elliot S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 10, 11.05.1999, p. 5604-5609.

Research output: Contribution to journalArticle

Detera-Wadleigh, SD, Badner, JA, Berrettini, WH, Yoshikawa, T, Goldin, LR, Turner, G, Rollins, DY, Moses, T, Sanders, AR, Karkera, JD, Esterling, LE, Zeng, J, Ferraro, TN, Guroff, JJ, Kazuba, D, Maxwell, ME, Nurnberger, J & Gershon, ES 1999, 'A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 10, pp. 5604-5609. https://doi.org/10.1073/pnas.96.10.5604
Detera-Wadleigh, Sevilla D. ; Badner, Judith A. ; Berrettini, Wade H. ; Yoshikawa, Takeo ; Goldin, Lynn R. ; Turner, Gordon ; Rollins, Denise Y. ; Moses, Tracy ; Sanders, Alan R. ; Karkera, Jayaprakash D. ; Esterling, Lisa E. ; Zeng, Jin ; Ferraro, Thomas N. ; Guroff, Juliet J. ; Kazuba, Diane ; Maxwell, Mary E. ; Nurnberger, John ; Gershon, Elliot S. / A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 10. pp. 5604-5609.
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abstract = "Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on ≃396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0.000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder. Suggestive linkage was found on 1q31-q32 (lod = 2.67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054). Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0.00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.",
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T1 - A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2

AU - Detera-Wadleigh, Sevilla D.

AU - Badner, Judith A.

AU - Berrettini, Wade H.

AU - Yoshikawa, Takeo

AU - Goldin, Lynn R.

AU - Turner, Gordon

AU - Rollins, Denise Y.

AU - Moses, Tracy

AU - Sanders, Alan R.

AU - Karkera, Jayaprakash D.

AU - Esterling, Lisa E.

AU - Zeng, Jin

AU - Ferraro, Thomas N.

AU - Guroff, Juliet J.

AU - Kazuba, Diane

AU - Maxwell, Mary E.

AU - Nurnberger, John

AU - Gershon, Elliot S.

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N2 - Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on ≃396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0.000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder. Suggestive linkage was found on 1q31-q32 (lod = 2.67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054). Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0.00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.

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