Non-coding structural variation differentially impacts attention-deficit hyperactivity disorder (ADHD) gene networks in African American vs Caucasian children.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
10
01
2020
accepted:
16
06
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Previous studies of attention-deficit hyperactivity disorder (ADHD) have suggested that structural variants (SVs) play an important role but these were mainly studied in subjects of European ancestry and focused on coding regions. In this study, we sought to address the role of SVs in non-European populations and outside of coding regions. To that end, we generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The ADHD cases included 116 African Americans (AA) and 89 of European Ancestry (EA) with SVs in comparison with 408 AA and 262 controls, respectively. Multiple SVs and target genes that associated with ADHD from previous studies were identified or replicated, and novel recurrent ADHD-associated SV loci were discovered. We identified clustering of non-coding SVs around neuroactive ligand-receptor interaction pathways, which are involved in neuronal brain function, and highly relevant to ADHD pathogenesis and regulation of gene expression related to specific ADHD phenotypes. There was little overlap (around 6%) in the genes impacted by SVs between AA and EA. These results suggest that SVs within non-coding regions may play an important role in ADHD development and that WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD.
Identifiants
pubmed: 32943653
doi: 10.1038/s41598-020-71307-0
pii: 10.1038/s41598-020-71307-0
pmc: PMC7499198
doi:
Substances chimiques
RNA, Untranslated
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15252Références
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