title: Re-sequencing of ankyrin 3 exon 48 and case-control association analysis of rare variants in bipolar disorder type I.
abstract: OBJECTIVE
  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.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Doyle
authors.forename: Alison T
authors.initials: AT
authors.lastname: Lai
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chou
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Wang
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gai
authors.forename: Eric F
authors.initials: EF
authors.lastname: Rappaport
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D017487:Ankyrins / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins