Dense SNP association study for bipolar I disorder on chromosome 18p11 suggests two loci with excess paternal transmission

J. G. Mulle, M. D. Fallin, V. K. Lasseter, J. A. McGrath, P. S. Wolyniec, A. E. Pulver

Research output: Contribution to journalArticle

Abstract

Parent-of-origin effects have been implicated as mediators of genetic susceptibility for a number of complex disease phenotypes, including bipolar disorder. Specifically, evidence for linkage on chromosome 18 is modified when allelic parent-of-origin is accommodated in the analysis. Our goal was to characterize the susceptibility locus for bipolar I disorder on chromosome 18p11 and investigate this parent-of-origin hypothesis in an association context. This was achieved by genotyping single nucleotide polymorphisms (SNPs) at a high density (1 SNP/5 kb) along 13.6 megabases of the linkage region. To increase our ability to detect a susceptibility locus, we restricted the phenotype definition to include only bipolar I probands. We also restricted our study population to Ashkenazi Jewish individuals; this population has characteristics of a genetic isolate and may therefore facilitate detection of variants for complex disease. Three hundred and forty-four pedigrees (363 parent/child trios) where probands were affected with bipolar 1 disorder were genotyped. Transmission disequilibrium test analysis revealed no statistically significant association to SNPs or haplotypes within this region in this sample. However, when parent-of-origin of transmitted SNPs was taken into account, suggestive association was revealed for two separate loci.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalMolecular psychiatry
Volume12
Issue number4
DOIs
StatePublished - Apr 30 2007

Keywords

  • 18p11
  • Bipolar disorder
  • Genetic association
  • Parent of origin
  • Psychiatric genetics
  • Transmission disequilibrium

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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