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

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...

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Published inMolecular psychiatry Vol. 12; no. 4; pp. 367 - 375
Main Authors MULLE, J. G, FALLIN, M. D, LASSETER, V. K, MCGRATH, J. A, WOLYNIEC, P. S, PULVER, A. E
Format Journal Article
LanguageEnglish
Published Basingstoke Nature Publishing Group 01.04.2007
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Summary: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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ISSN:1359-4184
1476-5578
DOI:10.1038/sj.mp.4001916