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. 2003 Jul;73(1):107-14.
doi: 10.1086/376562. Epub 2003 May 27.

Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative

Danielle M Dick  1 , 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 Berrettini, William 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 Jr
Affiliations

Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative

Danielle M Dick et al. Am J Hum Genet. 2003 Jul.

Erratum in

  • Am J Hum Genet. 2003 Oct;73(4):979

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.

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Figures

Figure 1
Figure 1
LOD score graphs from affected-relative-pair analyses across all chromosomes and diagnostic models (see key in figure). Tick labels on graphs indicate the placement of markers. Horizontal dashed line indicates the genomewide significance level, determined by simulation in this sample.
Figure 1
Figure 1
LOD score graphs from affected-relative-pair analyses across all chromosomes and diagnostic models (see key in figure). Tick labels on graphs indicate the placement of markers. Horizontal dashed line indicates the genomewide significance level, determined by simulation in this sample.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Center for Inherited Disease Research, http://www.cidr.jhmi.edu (for detailed information on laboratory methods and markers)
    1. Marshfield Center for Medical Genetics, http://research.marshfieldclinic.org/genetics/
    1. World Health Organization, http://www.who.int/whr/2002/whr2002_annex3.pdf (for World Health Report 2002)

References

    1. Abecasis GR, Cerny SS, Cookson WO, Cardon LR (2002) Merlin: rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101 - PubMed
    1. American Psychiatric Association (1994) DSM-IV: Diagnostic and statistical manual of mental disorders, 4th ed. American Psychiatric Association, Washington, DC
    1. Badner JA, Gershon ES (2002) Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7:405–411 - PubMed
    1. Bennett P, Segurado R, Jones I, Bort S, McCandless F, Lambert D, Heron J, Comerford C, Middle F, Corvin A, Pelios G, Kirov G, Larsen B, Mulcahy T, Williams N, O′Connell R, O′Mahony E, Payne A, Owen M, Holmans P, Craddock N, Gill M (2002). The Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report. Mol Psychiatry 7:189–200 - PubMed
    1. Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S, Nurnberger JI Jr, Gershon ES (1994) Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene. Proc Natl Acad Sci 91:5918–5921 - PMC - PubMed

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