title: Genome-wide study identifies PTPRO and WDR72 and FOXQ1-SUMO1P1 interaction associated with neurocognitive function.
abstract: BACKGROUND
  Several aspects of neurocognitive function have high heritability, but the molecular genetic mechanisms underlying neurocognition are not known. We performed a genome-wide association study (GWAS) to identify genes associated with neurocognition.
  
  
  METHODS
  700 Subjects (schizophrenia spectrum disorder, n=190, bipolar disorder n=157 and healthy individuals n=353) were tested with an extensive neuropsychological test battery, and genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0. After quality control, linear regression analysis of each of the 24 cognitive tests on the SNP dosage was performed, including age, gender, education and disease group as covariates. Additionally, 9 SNPs trending toward genome-wide significance were considered for epistatic interactions.
  
  
  RESULTS
  Four SNPs and 2 independent association signals achieving genome-wide significance were identified. Three intronic SNPs in PTPRO were associated with learning and memory (CVLT-II LDFR) (rs17222089, p=1.55×10(-8); rs11056571, p=1.68×10(-8); and rs2300290, p=1.09×10(-8)). rs719714 downstream of WDR72 was associated with executive functioning (CW-3: Inhibition, D-KEFS) (p=4.32×10(-8)). A highly significant epistatic interaction was found between rs9378605 upstream of FOXQ1 and rs11699311 downstream of SUMO1P1 for the Grooved Pegboard test (p=7.6×10(-14)).
  
  
  CONCLUSIONS
  We identified four novel loci associated with neurocognitive function and one novel epistatic interaction. The findings should be replicated in independent samples, but indicate a role of PTPRO in learning and memory, WDR72 with executive functioning, and an interaction between FOXQ1 and SUMO1P1 for psychomotor speed.
authors: Epi-Gen, Institute of Clinical Medicine, Akershus University Hospital, University of Oslo, Oslo, Norway. marissa.leblanc@medisin.uio.no
authors: Marissa
authors: M
authors: LeBlanc
authors: Bettina
authors: B
authors: Kulle
authors: Kjetil
authors: K
authors: Sundet
authors: Ingrid
authors: I
authors: Agartz
authors: Ingrid
authors: I
authors: Melle
authors: Srdjan
authors: S
authors: Djurovic
authors: Arnoldo
authors: A
authors: Frigessi
authors: Ole A
authors: OA
authors: Andreassen
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D056344:Executive Function / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics*; D025842:SUMO-1 Protein / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000235:genetics
chemical_list: C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors; D011506:Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C545712:WDR72 protein, human; C516888:PTPRO protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3