title: The cognitive impact of the ANK3 risk variant for bipolar disorder: initial evidence of selectivity to signal detection during sustained attention.
abstract: BACKGROUND
  Abnormalities in cognition have been reported in patients with Bipolar Disorder (BD) and their first degree relatives, suggesting that susceptibility genes for BD may impact on cognitive processes. Recent genome-wide genetic studies have reported a strong association with BD in a single nucleotide polymorphism (SNP) (rs10994336) within ANK3, which codes for Ankyrin 3. This protein is involved in facilitating the propagation of action potentials by regulating the assembly of sodium gated ion channels. Since ANK3 influences the efficiency of transmission of neuronal impulses, allelic variation in this gene may have widespread cognitive effects. Preclinical data suggest that this may principally apply to sequential signal detection, a core process of sustained attention.
  
  
  RESULTS
  One hundred and eighty-nine individuals of white British descent were genotyped for the ANK3 rs10994336 polymorphism and received diagnostic interviews and comprehensive neurocognitive assessment of their general intellectual ability, memory, decision making, response inhibition and sustained attention. Participants comprised euthymic BD patients (n = 47), their unaffected first-degree relatives (n = 75) and healthy controls (n = 67). The risk allele T was associated with reduced sensitivity in target detection (p = 0.0004) and increased errors of commission (p = 0.0018) during sustained attention regardless of diagnosis. We found no effect of the ANK3 genotype on general intellectual ability, memory, decision making and response inhibition.
  
  
  CONCLUSIONS
  Our results suggest that allelic variation in ANK3 impacts cognitive processes associated with signal detection and this mechanism may relate to risk for BD. However, our results require independent replication and confirmation that ANK3 (rs10994336) is a direct functional variant.
authors.affiliation: Section of Neurobiology of Psychosis, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Gaia
authors.initials: G
authors.lastname: Ruberto
authors.forename: Evangelos
authors.initials: E
authors.lastname: Vassos
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Roberto
authors.initials: R
authors.lastname: Tatarelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.forename: David
authors.initials: D
authors.lastname: Collier
authors.forename: Sophia
authors.initials: S
authors.lastname: Frangou
mesh_terms: D017487:Ankyrins / Q000235:genetics*; D001288:Attention; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins