title: New suggestive genetic loci and biological pathways for attention function in adult attention-deficit/hyperactivity disorder.
abstract: Attention deficit is one of the core symptoms of the attention-deficit/hyperactivity disorder (ADHD). However, the specific genetic variants that may be associated with attention function in adult ADHD remain largely unknown. The present study aimed to identifying SNPs associated with attention function in adult ADHD and tested whether these associations were enriched for specific biological pathways. Commissions, hit-reaction time (HRT), the standard error of HRT (HRTSE), and intraindividual coefficient variability (ICV) of the Conners Continuous Performance Test (CPT-II) were assessed in 479 unmedicated adult ADHD individuals. A Genome-Wide Association Study (GWAS) was conducted for each outcome and, subsequently, gene set enrichment analyses were performed. Although no SNPs reached genome-wide significance (P < 5E-08), 27 loci showed suggestive evidence of association with the CPT outcomes (P < E-05). The most relevant associated SNP was located in the SORCS2 gene (P = 3.65E-07), previously associated with bipolar disorder (BP), Alzheimer disease (AD), and brain structure in elderly individuals. We detected other genes suggested to be involved in synaptic plasticity, cognitive function, neurological and neuropsychiatric disorders, and smoking behavior such as NUAK1, FGF20, NETO1, BTBD9, DLG2, TOP3B, and CHRNB4. Also, several of the pathways nominally associated with the CPT outcomes are relevant for ADHD such as the ubiquitin proteasome, neurodegenerative disorders, axon guidance, and AD amyloid secretase pathways. To our knowledge, this is the first GWAS and pathway analysis of attention function in patients with persistent ADHD. Overall, our findings reinforce the conceptualization of attention function as a potential endophenotype for studying the molecular basis of adult ADHD. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Alemany
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.|Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ribasés
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Vilor-Tejedor
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.|Center for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.|Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Mora
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bosch
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.|Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Richarte
authors.affiliation: Facultat de Biologia, Departament de Genètica, Universitat de Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain.
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.|Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Casas
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.|Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Ramos-Quiroga
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
keywords: Attention-deficit/hyperactivity disorder; Conners Continuous Performance Test; GWAS; SORCS2; adults