Initial genomic scan of the NIMH genetics initiative bipolar pedigrees

Chromosomes 3, 5, 15, 16, 17, and 22

Howard Edenberg, Tatiana Foroud, P. Michael Conneally, Jeffrey J. Sorbel, Kristie Carr, Candice Crose, Chris Willig, Jinghua Zhao, Marvin Miller, Elizabeth Bowman, Aimee Mayeda, N. Leela Rau, Carrie Smiley, John P. Rice, Alison Goate, Theodore Reich, O. Colin Stine, Francis McMahon, J. Raymond DePaulo, Deborah Meyers & 5 others Sevilla D. Detera-Wadleigh, Lynn R. Goldin, Elliot S. Gershon, Mary C. Blehar, John Nurnberger

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16, 17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (0) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S 1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage.

Original languageEnglish
Pages (from-to)238-246
Number of pages9
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 5
Chromosomes, Human, Pair 3
Pedigree
Alleles
Bipolar Disorder
Chromosomes
Chromosomes, Human, Pair 22
DNA
Telomere

Keywords

  • Family study
  • Genetic linkage
  • Microsatellite markers
  • Sib pair analysis
  • Unipolar recurrent depression

ASJC Scopus subject areas

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

Cite this

Initial genomic scan of the NIMH genetics initiative bipolar pedigrees : Chromosomes 3, 5, 15, 16, 17, and 22. / Edenberg, Howard; Foroud, Tatiana; Conneally, P. Michael; Sorbel, Jeffrey J.; Carr, Kristie; Crose, Candice; Willig, Chris; Zhao, Jinghua; Miller, Marvin; Bowman, Elizabeth; Mayeda, Aimee; Rau, N. Leela; Smiley, Carrie; Rice, John P.; Goate, Alison; Reich, Theodore; Stine, O. Colin; McMahon, Francis; DePaulo, J. Raymond; Meyers, Deborah; Detera-Wadleigh, Sevilla D.; Goldin, Lynn R.; Gershon, Elliot S.; Blehar, Mary C.; Nurnberger, John.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 74, No. 3, 1997, p. 238-246.

Research output: Contribution to journalArticle

Edenberg, H, Foroud, T, Conneally, PM, Sorbel, JJ, Carr, K, Crose, C, Willig, C, Zhao, J, Miller, M, Bowman, E, Mayeda, A, Rau, NL, Smiley, C, Rice, JP, Goate, A, Reich, T, Stine, OC, McMahon, F, DePaulo, JR, Meyers, D, Detera-Wadleigh, SD, Goldin, LR, Gershon, ES, Blehar, MC & Nurnberger, J 1997, 'Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: Chromosomes 3, 5, 15, 16, 17, and 22', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 74, no. 3, pp. 238-246. https://doi.org/10.1002/(SICI)1096-8628(19970531)74:3<238::AID-AJMG2>3.0.CO;2-M
Edenberg, Howard ; Foroud, Tatiana ; Conneally, P. Michael ; Sorbel, Jeffrey J. ; Carr, Kristie ; Crose, Candice ; Willig, Chris ; Zhao, Jinghua ; Miller, Marvin ; Bowman, Elizabeth ; Mayeda, Aimee ; Rau, N. Leela ; Smiley, Carrie ; Rice, John P. ; Goate, Alison ; Reich, Theodore ; Stine, O. Colin ; McMahon, Francis ; DePaulo, J. Raymond ; Meyers, Deborah ; Detera-Wadleigh, Sevilla D. ; Goldin, Lynn R. ; Gershon, Elliot S. ; Blehar, Mary C. ; Nurnberger, John. / Initial genomic scan of the NIMH genetics initiative bipolar pedigrees : Chromosomes 3, 5, 15, 16, 17, and 22. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 1997 ; Vol. 74, No. 3. pp. 238-246.
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abstract = "As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16, 17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (0) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S 1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage.",
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AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Conneally, P. Michael

AU - Sorbel, Jeffrey J.

AU - Carr, Kristie

AU - Crose, Candice

AU - Willig, Chris

AU - Zhao, Jinghua

AU - Miller, Marvin

AU - Bowman, Elizabeth

AU - Mayeda, Aimee

AU - Rau, N. Leela

AU - Smiley, Carrie

AU - Rice, John P.

AU - Goate, Alison

AU - Reich, Theodore

AU - Stine, O. Colin

AU - McMahon, Francis

AU - DePaulo, J. Raymond

AU - Meyers, Deborah

AU - Detera-Wadleigh, Sevilla D.

AU - Goldin, Lynn R.

AU - Gershon, Elliot S.

AU - Blehar, Mary C.

AU - Nurnberger, John

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