A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children

作者：Alemany Silvia; Vilor Tejedor Natalia; Bustamante Mariona; Pujol Jesus; Macia Didac; Martinez Vilavella Gerard; Fenoll Raquel; Alvarez Pedrerol Mar; Forns Joan; Julvez Jordi; Suades Gonzalez Elisabet; Llop Sabrina; Rebagliato Marisa; Sunyer Jordi

来源：PLos One, 2016, 11(9): e0163048.

DOI：10.1371/journal.pone.0163048

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 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.

• 出版日期2016-9-22