Initial genome scan of the nimh genetics initiative bipolar pedigrees: Chromosomes 1, 6, 8, 10, and 12

John P. Rice, Alison Goate, Jeff T. Williams, Laura Bierut, David Dorr, William Wu, Shantia Shears, Gayathri Gopalakrishnan, Howard J. Edenberg, Tatiana Foroud, John Nurnberger, Elliot S. Gershon, Sevilla D. Detera-Wadleigh, Lynn R. Goldin, Juliet J. Guroff, Francis J. McMahon, Sylvia Simpson, Dean MacKinnon, Melvin McInnis, O. Colin StineJ. Raymond DePaulo, Mary C. Blehar, Theodore Reich

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

A report on an initial genome screen on 540 individuals in 97 families was collected as part of the NIMH Genetics Initiative on Bipolar Disorder. Families were ascertained to be informative for genetic linkage and underwent a common ascertainment and assessment protocol at four clinical sites. The sample was genotyped for 65 highly polymorphic markers from chromosomes 1, 6, 8, 10, and 12. The average intermarker interval was 16 cM. Genotypic data was analyzed using affected sib pair, multipoint affected sib pair, and pedigree analysis methods. Multipoint methods gave lod scores of approximately two on chromosomes 1, 6, and 10. The peak lod score on chromosome 6 occurred at the end of the q-arm, at some distance from the 6p24-22 area previously implicated for schizophrenia. We are currently genotyping additional markers to reduce the intermarker interval around the signals. The interpretation of results from a genome screen of a complex disorder and the problem of achieving a balance between detecting false positive results and the ability to detect genes of modest effect are discussed.

Original languageEnglish
Pages (from-to)247-253
Number of pages7
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume74
Issue number3
DOIs
StatePublished - 1997

Keywords

  • Affected sib pairs
  • Bipolar disorder
  • Genome scan
  • Genome screen
  • Linkage analysis

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