Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees

Chromosomes 2, 11, 13, 14, and x

O. Colin Stine, Francis J. McMahon, Li Shiun Chen, Jianfeng Xu, Deborah A. Meyers, Dean F. MacKinnon, Sylvia Simpson, Melvin G. McInnis, John P. Rice, Alison Goate, Theodore Reich, Howard Edenberg, Tatiana Foroud, John Nurnberger, Sevilla D. Detera-Wadleigh, Lynn R. Goldin, Juliet Guroff, Elliot S. Gershon, Mary C. Blehar, J. Raymond DePaulo

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk λ(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring λ(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with λ(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the markers in Xp22 would have λ(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have λ(i) ≤ 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume74
Issue number3
DOIs
StatePublished - 1997

Fingerprint

National Institute of Mental Health (U.S.)
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 2
Pedigree
Bipolar Disorder
Genome
Chromosomes, Human, Pair 14
Major Depressive Disorder
X Chromosome
Psychotic Disorders

Keywords

  • Affective disorder
  • Linkage
  • Occlusion mapping

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees : Chromosomes 2, 11, 13, 14, and x. / Stine, O. Colin; McMahon, Francis J.; Chen, Li Shiun; Xu, Jianfeng; Meyers, Deborah A.; MacKinnon, Dean F.; Simpson, Sylvia; McInnis, Melvin G.; Rice, John P.; Goate, Alison; Reich, Theodore; Edenberg, Howard; Foroud, Tatiana; Nurnberger, John; Detera-Wadleigh, Sevilla D.; Goldin, Lynn R.; Guroff, Juliet; Gershon, Elliot S.; Blehar, Mary C.; DePaulo, J. Raymond.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 74, No. 3, 1997, p. 263-269.

Research output: Contribution to journalArticle

Stine, OC, McMahon, FJ, Chen, LS, Xu, J, Meyers, DA, MacKinnon, DF, Simpson, S, McInnis, MG, Rice, JP, Goate, A, Reich, T, Edenberg, H, Foroud, T, Nurnberger, J, Detera-Wadleigh, SD, Goldin, LR, Guroff, J, Gershon, ES, Blehar, MC & DePaulo, JR 1997, 'Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: Chromosomes 2, 11, 13, 14, and x', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 74, no. 3, pp. 263-269. https://doi.org/10.1002/(SICI)1096-8628(19970531)74:3<263::AID-AJMG5>3.0.CO;2-R
Stine, O. Colin ; McMahon, Francis J. ; Chen, Li Shiun ; Xu, Jianfeng ; Meyers, Deborah A. ; MacKinnon, Dean F. ; Simpson, Sylvia ; McInnis, Melvin G. ; Rice, John P. ; Goate, Alison ; Reich, Theodore ; Edenberg, Howard ; Foroud, Tatiana ; Nurnberger, John ; Detera-Wadleigh, Sevilla D. ; Goldin, Lynn R. ; Guroff, Juliet ; Gershon, Elliot S. ; Blehar, Mary C. ; DePaulo, J. Raymond. / Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees : Chromosomes 2, 11, 13, 14, and x. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 1997 ; Vol. 74, No. 3. pp. 263-269.
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T2 - Chromosomes 2, 11, 13, 14, and x

AU - Stine, O. Colin

AU - McMahon, Francis J.

AU - Chen, Li Shiun

AU - Xu, Jianfeng

AU - Meyers, Deborah A.

AU - MacKinnon, Dean F.

AU - Simpson, Sylvia

AU - McInnis, Melvin G.

AU - Rice, John P.

AU - Goate, Alison

AU - Reich, Theodore

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Nurnberger, John

AU - Detera-Wadleigh, Sevilla D.

AU - Goldin, Lynn R.

AU - Guroff, Juliet

AU - Gershon, Elliot S.

AU - Blehar, Mary C.

AU - DePaulo, J. Raymond

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