Re-sequencing of ankyrin 3 exon 48 and case-control association analysis of rare variants in bipolar disorder type I Journal Article

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Authors: Doyle, G. A.; Lai, A. T.; Chou, A. D.; Wang, M. J.; Gai, X.; Rappaport, E. F.; Berrettini, W. H.
Article Title: Re-sequencing of ankyrin 3 exon 48 and case-control association analysis of rare variants in bipolar disorder type I
Abstract: OBJECTIVES: Genome-wide association studies (GWAS) recently identified ankyrin 3 (ANK3) as a candidate gene for bipolar disorder type I (BPD-I). Because the GWAS suggested multiple common haplotypes associated with BPD-I (with odds ratio ~1.3), we hypothesized that rare variants within these common haplotypes might increase risk for BPD-I. METHODS: We undertook a project in which the serine-rich domain-tail domain (SRD-TD)-encoding exon of ANK3 was amplified from genomic DNA (gDNA) of 384 BPD-I patients and re-sequenced by next generation sequencing (NGS; SOLiD). RESULTS: We confirmed 18 novel mis-sense rare variants and one novel insertion/deletion variant within the SRD-TD exon, many of which change amino acid residues with extremely high evolutionary conservation. We genotyped most of these mis-sense variants in >/= 1000 BPD-I and >/= 1000 control individuals. We found no statistically significant association of any of the rare variants detected with BPD-I. CONCLUSIONS: Thus, we conclude that rare variants within the re-sequenced structural domains of ANK3 exon 48 do not contribute to BPD-I.
Journal Title: Bipolar disorders
Volume: 14
Issue: 8
ISSN: 1399-5618; 1398-5647
Publisher: Wiley Periodicals, Inc  
Journal Place: Denmark
Date Published: 2012
Start Page: 809
End Page: 821
Language: eng
DOI/URL:

10.1111/bdi.12002

10.1111/bdi.12002
Notes: CI: (c) 2012; JID: 100883596; 0 (ANK3 protein, human); 0 (Ankyrins); 2012/09/11 [aheadofprint]; ppublish