期刊
NPJ GENOMIC MEDICINE
卷 4, 期 -, 页码 -出版社
SPRINGER NATURE, CO-PUBL CTR EXCELLENCE GENOMIC MED RES
DOI: 10.1038/s41525-019-0098-3
关键词
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资金
- Genome Canada
- Canada Foundation for Innovation
- Canadian Institute for Advanced Research
- Government of Ontario
- Canadian Institutes of Health Research
- Hospital for Sick Children Foundation
- Ontario Brain Institute (OBI)/The Province of Ontario Neurodevelopmental Disorders Network (POND)
- Autism Speaks
- University of Toronto McLaughlin Centre
- Canadian Institutes of Health Research [MOP-209699, MOP-192190]
- OBI [IDS-II-02]
- National Institute of Mental Health [R01MH085321, R01MH101493]
- Children's Foundation of Michigan
- Lycaki-Young funds State of Michigan
- Miriam Hamburger Endowment
- Paul and Anita Strauss Endowment
- NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]
- Gene Environment Association Studies (GENEVA) under GEI
- GENEVA Coordinating Center [U01 HG004446]
- Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]
- Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]
- Family Study of Cocaine Dependence (FSCD) [R01 DA013423]
- NIH GEI [U01HG004438]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH contract High throughput genotyping for studying the genetic contributions to human disease [HHSN268200782096C]
- National Institutes of Health [HHSN268200782096C]
- Gene Environment Association Studies (GENEVA) Coordinating Center [U01 HG004446]
- University of Wisconsin Transdisciplinary Tobacco Use Research Center [P50 DA019706, P50 CA084724]
- National Eye Institute
- Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA, NIA
- [1 x 01 HG005274-01]
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 (43%) 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 NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.
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