A large data resource of genomic copy number variation across neurodevelopmental disorders.
Molecular medicine
Neurodevelopmental disorders
Pathogenesis
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
2019
2019
Historique:
received:
06
05
2019
accepted:
05
09
2019
entrez:
12
10
2019
pubmed:
12
10
2019
medline:
12
10
2019
Statut:
epublish
Résumé
Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are
Identifiants
pubmed: 31602316
doi: 10.1038/s41525-019-0098-3
pii: 98
pmc: PMC6779875
doi:
Types de publication
Journal Article
Langues
eng
Pagination
26Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG004438
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004446
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101493
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA089392
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA019706
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004422
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA013423
Pays : United States
Organisme : NIAAA NIH HHS
ID : U10 AA008401
Pays : United States
Organisme : NHGRI NIH HHS
ID : HHSN268200782096C
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085321
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA084724
Pays : United States
Informations de copyright
© The Author(s) 2019.
Déclaration de conflit d'intérêts
Competing interestsS.W.S. serves on the Scientific Advisory Committees of Population Bio and Deep Genomics; intellectual property originating from his research and held at the Hospital for Sick Children is licensed to Lineagen, and separately Athena Diagnostics. D.M. is a full-time employee of Deep Genomics and is entitled to a stock option. R.J.S., P.D.A., and J.C. consult for Highland Therapeutics. Intellectual property from ADHD research at the Hospital for Sick Children is licensed to Ehave and the National Research Council of Canada. Other authors declare no competing interests for the data and interpretation presented in this study. R.J.S., P.D.A., and J.C. consults for Highland Therapeutics. Intellectual property from their research at the Hospital for Sick Children is licensed to Ehave and the National Research Council. D.M. is a full-time employee of Deep Genomics and is entitled to stock options. S.W.S. is on the Scientific Advisory Committees of Population Bio and Deep Genomics; intellectual property from his research held at the Hospital for Sick Children is licensed to Athena Diagnostics, and separately to Lineagen. These relationships did not influence data interpretation or presentation during this study, but are disclosed for potential future consideration.
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