Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees

Tatiana Foroud, Peter F. Castelluccio, Daniel L. Koller, Howard J. Edenberg, Marvin Miller, Elizabeth Bowman, N. Leela Rau, Carrie Smiley, John P. Rice, Alison Goate, Christopher Armstrong, Laura J. Bierut, Theodore Reich, Sevilla D. Detera-Wadleigh, Lynn R. Goldin, Judith A. Badner, Juliet J. Guroff, Elliot S. Gershon, Francis J. McMahon, Sylvia SimpsonDean MacKinnon, Melvin McInnis, O. Colin Stine, J. Raymond DePaulo, Mary C. Blehar, John I. Nurnberger

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a genome screen using 365 markers was performed on 540 DNAs from 97 families, enriched for affected relative pairs. This is the largest uniformly ascertained and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SABP), 72 with bipolar II (BPII), and 88 with unipolar recurrent depression (UPR). A hierarchical set of definitions of affected status was examined. Under Model I, affected individuals were those with a diagnosis of BPI or SABP, Model II included as affected those fitting Model I plus BPII, and Model III included those fitting Model II plus UPR. This data set was previously analyzed using primarily affected sib pair methods. We report the results of nonparametric linkage analyses of the extended pedigree structure using the program Genehunter Plus. The strongest finding was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II. This region has been previously implicated in genome- wide studies of schizophrenia and bipolar disorder. Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)18-23
Number of pages6
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume96
Issue number1
DOIs
StatePublished - Feb 7 2000

Keywords

  • Bipolar affective disorder
  • Genetics
  • Genomic survey
  • Linkage
  • Nonparametric analysis

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