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

Molecular Psychiatry volume 12, pages 367–375 (2007)Cite this article

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.

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Authors and Affiliations

  1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

    J G Mulle

  2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    M D Fallin

  3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

    V K Lasseter, J A McGrath, P S Wolyniec & A E Pulver

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  1. J G Mulle
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Correspondence to A E Pulver.

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Mulle, J., Fallin, M., Lasseter, V. et al. Dense SNP association study for bipolar I disorder on chromosome 18p11 suggests two loci with excess paternal transmission. Mol Psychiatry 12, 367–375 (2007). https://doi.org/10.1038/sj.mp.4001916

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