Montanucci, Ludovica; Lewis-Smith, David; Collins, Ryan L; Niestroj, Lisa-Marie; Parthasarathy, Shridhar; Xian, Julie; Ganesan, Shiva; Macnee, Marie; Brünger, Tobias; Thomas, Rhys H; Talkowski, Michael; Helbig, Ingo; Leu, Costin; Lal, Dennis (2023). Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals. Nature Communications, 14(1), p. 4392. Springer Nature 10.1038/s41467-023-39539-6
|
Text
s41467-023-39539-6.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview |
Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Human Genetics |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
André Schaller |
Date Deposited: |
04 Jan 2024 11:33 |
Last Modified: |
04 Jan 2024 11:40 |
Publisher DOI: |
10.1038/s41467-023-39539-6 |
PubMed ID: |
37474567 |
Additional Information: |
André Schaller is part of the Collaborators: Epi25 Collaborative |
BORIS DOI: |
10.48350/189664 |
URI: |
https://boris.unibe.ch/id/eprint/189664 |
Actions (login required)
 |
Edit item |