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.

• Authors: Glenn A Doyle, Alison T Lai, Andrew D Chou, Min-Jung Wang, Xiaowu Gai, Eric F Rappaport, Wade H Berrettini
• Journal: Bipolar disorders (Bipolar Disord) Vol. 14 Issue 8 Pg. 809-21 (Dec 2012) ISSN: 1399-5618 [Electronic] Denmark
• PMID: 22966748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley and Sons A/S.

Chemical References

• ANK3 protein, human
• Ankyrins

Topics

• Ankyrins (genetics)
• Bipolar Disorder (genetics)
• Case-Control Studies
• Exons (genetics)
• Family Health
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Polymorphism, Single Nucleotide (genetics)
• Psychiatric Status Rating Scales
• Reproducibility of Results
• Sequence Analysis, DNA