title: A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children.
abstract: BACKGROUND
  Attention function filters and selects behaviorally relevant information. This capacity is impaired in some psychiatric disorders and has been proposed as an endophenotype for Attention-Deficit/Hyperactivity Disorder; however, its genetic basis remains largely unknown. This study aimed to identify single nucleotide polymorphism (SNPs) associated with attention function.
  
  
  METHODS
  The discovery sample included 1655 children (7-12 years) and the replication sample included 546 children (5-8 years). Five attention outcomes were assessed using the computerized Attentional Network Test (ANT): alerting, orienting, executive attention, Hit Reaction time (HRT) and the standard error of HRT (HRTSE). A Genome-wide Association Study was conducted for each outcome. Gene set enrichment analyses were performed to detect biological pathways associated with attention outcomes. Additional neuroimaging analyses were conducted to test neural effects of detected SNPs of interest.
  
  
  RESULTS
  Thirteen loci showed suggestive evidence of association with attention function (P<10-5) in the discovery sample. One of them, the rs4321351 located in the PID1 gene, was nominally significant in the replication sample although it did not survive multiple testing correction. Neuroimaging analysis revealed a significant association between this SNP and brain structure and function involving the frontal-basal ganglia circuits. The mTOR signaling and Alzheimer disease-amyloid secretase pathways were significantly enriched for alerting, orienting and HRT respectively (FDR<5%).
  
  
  CONCLUSIONS
  These results suggest for the first time the involvement of the PID1 gene, mTOR signaling and Alzheimer disease-amyloid secretase pathways, in attention function during childhood. These genes and pathways have been proposed to play a role in neuronal plasticity, memory and neurodegenerative disease.
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
authors.forename: Silvia
authors.identifier: http://orcid.org/0000-0002-7925-6767
authors.initials: S
authors.lastname: Alemany
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Vilor-Tejedor
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.affiliation: MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.|Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM G21, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pujol
authors.affiliation: MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.
authors.forename: Dídac
authors.initials: D
authors.lastname: Macià
authors.affiliation: MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Martínez-Vilavella
authors.affiliation: MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fenoll
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Alvárez-Pedrerol
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Joan
authors.initials: J
authors.lastname: Forns
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Júlvez
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Learning Disabilities Unit (UTAE); Neuropediatrics Department, Hospital de Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Suades-González
authors.affiliation: CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Llop
authors.affiliation: CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain.|University Jaime I (UJI), Castellón, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Rebagliato
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer