Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20

Jessica Ross, Wade Berrettini, William Coryell, Elliot S. Gershon, Judith A. Badner, John R. Kelsoe, Melvin G. McInnis, Francis J. McMahon, Dennis L. Murphy, John I. Nurnberger, Tatiana Foroud, John P. Rice, William B. Scheftner, Peter Zandi, Howard Edenberg, William Byerley

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

OBJECTIVE: Our aim is to map chromosomal regions that harbor loci that increase susceptibility to bipolar disorder. METHODS: We analyzed 644 bipolar families ascertained by the National Institute of Mental Health Human Genetics Initiative for bipolar disorder. The families have been genotyped with microsatellite loci spaced every approximately 10cM or less across the genome. Earlier analyses of these pedigrees have been limited to nonparametric (model-free) methods and thus, information from unaffected subjects with genotypes was not considered. In this study, we used parametric analyses assuming dominant and recessive transmission and specifying a maximum penetrance of 70%, so that information from unaffecteds could be weighed in the linkage analyses. As in previous linkage analyses of these pedigrees, we analyzed three diagnostic categories: model 1 included only bipolar I and schizoaffective, bipolar cases (1565 patients of whom approximately 4% were schizoaffective, bipolar); model 2 included all individuals in model 1 plus bipolar II patients (1764 total individuals); and model 3 included all individuals in model 2 with the addition of patients with recurrent major depressive disorder (2046 total persons). RESULTS: Assuming dominant inheritance the highest genome-wide pair-wise logarithm of the odds (LOD) score was 3.2 with D16S749 using model 2 patients. Multipoint analyses of this region yielded a maximum LOD score of 4.91. Under recessive transmission a number of chromosome 20 markers were positive and multipoint analyses of the area gave a maximum LOD of 3.0 with model 2 cases. CONCLUSION: The chromosome 16p and 20 regions have been implicated by some studies and the data reported herein provide additional suggestive evidence of bipolar susceptibility genes in these regions.

Original languageEnglish (US)
Pages (from-to)191-198
Number of pages8
JournalPsychiatric genetics
Volume18
Issue number4
DOIs
StatePublished - Aug 2008

Keywords

  • Bipolar disorder
  • Chromosome 16
  • Chromosome 20
  • Complex disorder
  • Gene mapping
  • Genetics
  • Linkage analysis
  • Parametric analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Genetics
  • Biological Psychiatry
  • Neuroscience(all)

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