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Linkage disequilibrium mapping of bipolar affective disorder at 12q23-q24 provides evidence for association at CUX2 and FLJ32356

Glaser, B., Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Green, E., Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610 and Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 2005. Linkage disequilibrium mapping of bipolar affective disorder at 12q23-q24 provides evidence for association at CUX2 and FLJ32356. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 132B (1) , pp. 38-45. 10.1002/ajmg.b.30081

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Abstract

Chromosome 12q23-q24 has been implicated by several linkage studies as harboring a gene for bipolar affective disorder. We performed linkage disequilibrium (LD) mapping with 17 microsatellite markers across a 1.6 Mb-wide segment forming the central part of our narrowest linkage region. A significant signal (P = 0.0016) was identified for one microsatellite marker in our UK Caucasian case-control sample (347 cases, 374 controls). Genes, including regulatory elements, around this marker were screened for mutations and the LD structure of the region determined by genotyping 22 SNPs and insertion/deletion polymorphisms in 94 individuals. A set of 11 haplotype tagging (ht) SNPs was genotyped in our sample using a two-stage procedure. Two SNPs (rs3847953 and rs933399) and an insertion/deletion with putative functional relevance (which are in high LD with each other and with the microsatellite marker) showed significant or nearly significant association with bipolar disorder after Bonferroni-correction (reaching nominal P values from P = 0.002 to P = 0.005). In a sample of 110 UK Caucasian parent-offspring trios there was a trend for an over transmission in the same direction that failed to meet conventional levels of statistical significance. Our data provide evidence for association between bipolar mood disorder and markers on chromosome 12q23-q24 but need replication in independent samples.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: Wiley-Blackwell
ISSN: 1552-4841
Last Modified: 31 Oct 2022 10:05
URI: https://orca.cardiff.ac.uk/id/eprint/83597

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