title: The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis.
abstract: BACKGROUND
  Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients.
  
  
  METHODS
  In total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability.
  
  
  RESULTS
  Increased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1-3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis.
  
  
  CONCLUSIONS
  These data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Hargreaves
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Anney
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: C
authors.initials: C
authors.lastname: O'Dushlaine
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: K K
authors.initials: KK
authors.lastname: Nicodemus
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Gill
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Corvin
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Morris
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience,Trinity College Dublin,Republic of Ireland.
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
mesh_terms: D000328:Adult; D000483:Alleles; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D012559:Schizophrenia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D059848:HLA-DQ alpha-Chains