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Title: A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children
Author: Alemany, Silvia
Vilor-Tejedor, Natàlia
Bustamante Pineda, Mariona
Pujol, Jesus
Macià, Dídac
Martínez-Vilavella, Gerard
Fenoll, Raquel
Alvárez-Pedrerol, Mar
Forns, Joan
Julvez, Jordi
Suades-González, Elisabet
Llop, Sabrina
Rebagliato, Marisa
Sunyer Deu, Jordi
Keywords: Malaltia d'Alzheimer
Genètica humana
Alzheimer's disease
Human genetics
Issue Date: 22-Sep-2016
Publisher: Public Library of Science (PLoS)
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. MATERIALS AND 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%). CONCLUSION: 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.
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It is part of: PLoS One, 2016, vol. 11, num. 9, p. e0163048
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (ISGlobal)

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