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New suggestive genetic loci and biological pathways for attention function in adult attention‐deficit/hyperactivity disorder
Author(s) -
Alemany Silvia,
Ribasés Marta,
VilorTejedor Natàlia,
Bustamante Mariona,
SánchezMora Cristina,
Bosch Rosa,
Richarte Vanesa,
Cormand Bru,
Casas Miguel,
RamosQuiroga Josep A.,
Sunyer Jordi
Publication year - 2015
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32341
Subject(s) - endophenotype , genome wide association study , attention deficit hyperactivity disorder , psychology , bipolar disorder , single nucleotide polymorphism , genetic association , neuroscience , genetic architecture , genetics , clinical psychology , psychiatry , cognition , gene , phenotype , biology , genotype
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.