Genomewide linkage analyses of bipolar disorder: A new sample of 250 pedigrees from the national institute of mental health genetics initiative

Danielle M. Dick, Tatiana Foroud, Leah Flury, Elizabeth S. Bowman, Marvin J. Miller, N. Leela Rau, P. Ryan Moe, Nalini Samavedy, Rif El-Mallakh, Husseini Manji, Debra A. Glitz, Eric T. Meyer, Carrie Smiley, Rhoda Hahn, Clifford Widmark, Rebecca McKinney, Laura Sutton, Christos Ballas, Dorothy Grice, Wade BerrettiniWilliam Byerley, William Coryell, Raymond DePaulo, Dean F. MacKinnon, Elliot S. Gershon, John R. Kelsoe, Francis J. McMahon, Melvin McInnis, Dennis L. Murphy, Theodore Reich, William Scheftner, John I. Nurnberger

Research output: Contribution to journalArticle

Abstract

We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P < .05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P < .10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.

Original languageEnglish (US)
Pages (from-to)107-114
Number of pages8
JournalAmerican journal of human genetics
Volume73
Issue number1
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Dick, D. M., Foroud, T., Flury, L., Bowman, E. S., Miller, M. J., Rau, N. L., Moe, P. R., Samavedy, N., El-Mallakh, R., Manji, H., Glitz, D. A., Meyer, E. T., Smiley, C., Hahn, R., Widmark, C., McKinney, R., Sutton, L., Ballas, C., Grice, D., ... Nurnberger, J. I. (2003). Genomewide linkage analyses of bipolar disorder: A new sample of 250 pedigrees from the national institute of mental health genetics initiative. American journal of human genetics, 73(1), 107-114. https://doi.org/10.1086/376562