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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/102450
A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children
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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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ALEMANY SIERRA, Silvia, et al. A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children. PLoS One. 2016. Vol. 11, num. 9, pags. e0163048. ISSN 1932-6203. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/102450