Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals
Montanucci, L.; Lewis-Smith, D.; Collins, R. L.; Niestroj, L.-M.; Parthasarathy, S.; Xian, J. & Ganesan, S. et al. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-39539-6
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Details
- Authors Group
- Epi25 Collaborative
The authors list is uncomplete: - Authors
- Montanucci, Ludovica; Lewis-Smith, David; Collins, Ryan L.; Niestroj, Lisa-Marie; Parthasarathy, Shridhar; Xian, Julie; Ganesan, Shiva; Macnee, Marie; Brünger, Tobias; Thomas, Rhys H.; Lal, Dennis
- Abstract
- Abstract 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.
- Issue Date
- 2023
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English
- Sponsor
- Wellcome Trust https://doi.org/10.13039/100004440
National Science Foundation https://doi.org/10.13039/100000001
U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development https://doi.org/10.13039/100009633
Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659
U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences https://doi.org/10.13039/100006108