title: Polymorphisms of dopamine pathway genes NRG1 and LMX1A are associated with cognitive performance in bipolar disorder.
abstract: OBJECTIVE
  LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder.
  
  
  METHODS
  In total, four SNPs were directly genotyped. Regression models with five aggregated cognitive domains and intelligence quotient (IQ) score were run using risk variants of LMX1A (rs11809911, rs4657412, rs6668493) and NRG1 (rs35753505) as predictors. Models were performed in a clinical sample of patients with bipolar disorder (n = 114) and healthy controls (n = 104).
  
  
  RESULTS
  The risk variants of the rs11809911 SNP in LMX1A were negatively associated with IQ score and memory/learning, whereas the risk variants of rs35753505 in NRG1 were positively associated with IQ score (adjusted R(2) = 0.17, Q = 0.006) and memory/learning (adjusted R(2) = 0.24, Q = 0.001). The risk variants of the rs35753505 SNP in NRG1 were positively associated with language (adjusted R(2) = 0.11, Q = 0.006), visuospatial functions (adjusted R(2) = 0.23, Q = 0.001), and attention/speed (adjusted R(2) = 0.25, Q = 0.001). Results could not be replicated in controls.
  
  
  CONCLUSIONS
  The risk variants of the rs35753505 SNP were associated with increased performance in several cognitive domains and IQ, whereas the risk variants of the rs11809911 SNP in LMX1A was associated with reduced IQ and memory/learning.
authors.affiliation: Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Sindre
authors.identifier: http://orcid.org/0000-0001-5570-875X
authors.initials: S
authors.lastname: Rolstad
authors.affiliation: Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Ekman
authors.affiliation: Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Sellgren
authors.affiliation: Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007361:Intelligence Tests; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; C094131:NRG1 protein, human; D020890:Neuregulin-1; D014157:Transcription Factors; D004298:Dopamine
keywords: bipolar disorder; cognition; dopamine function hypothesis; single nucleotide polymorphisms