Title |
Copy number variation meta-analysis reveals a novel duplication at 9p24 associated with multiple neurodevelopmental disorders
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Published in |
Genome Medicine, November 2017
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DOI | 10.1186/s13073-017-0494-1 |
Pubmed ID | |
Authors |
Joseph T. Glessner, Jin Li, Dai Wang, Michael March, Leandro Lima, Akshatha Desai, Dexter Hadley, Charlly Kao, Raquel E. Gur, Nadine Cohen, Patrick M. A. Sleiman, Qingqin Li, Hakon Hakonarson, the Janssen-CHOP Neuropsychiatric Genomics Working Group |
Abstract |
Neurodevelopmental and neuropsychiatric disorders represent a wide spectrum of heterogeneous yet inter-related disease conditions. The overlapping clinical presentations of these diseases suggest a shared genetic etiology. We aim to identify shared structural variants spanning the spectrum of five neuropsychiatric disorders. We investigated copy number variations (CNVs) in five cohorts, including schizophrenia (SCZ), bipolar disease (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and depression, from 7849 cases and 10,799 controls. CNVs were called based on intensity data from genome-wide SNP arrays and CNV frequency was compared between cases and controls in each disease cohort separately. Meta-analysis was performed via a gene-based approach. Quantitative PCR (qPCR) was employed to validate novel significant loci. In our meta-analysis, two genes containing CNVs with exonic overlap reached genome-wide significance threshold of meta P value < 9.4 × 10-6 for deletions and 7.5 × 10-6 for duplications. We observed significant overlap between risk CNV loci across cohorts. In addition, we identified novel significant associations of DOCK8/KANK1 duplications (meta P value = 7.5 × 10-7) across all cohorts, and further validated the CNV region with qPCR. In the first large scale meta-analysis of CNVs across multiple neurodevelopmental/psychiatric diseases, we uncovered novel significant associations of structural variants in the locus of DOCK8/KANK1 shared by five diseases, suggesting common etiology of these clinically distinct neurodevelopmental conditions. |
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Country | Count | As % |
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United Kingdom | 3 | 25% |
Ireland | 1 | 8% |
Spain | 1 | 8% |
Unknown | 7 | 58% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 9 | 75% |
Scientists | 2 | 17% |
Science communicators (journalists, bloggers, editors) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 110 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 14 | 13% |
Student > Master | 14 | 13% |
Researcher | 11 | 10% |
Other | 10 | 9% |
Student > Bachelor | 7 | 6% |
Other | 17 | 15% |
Unknown | 37 | 34% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 20 | 18% |
Biochemistry, Genetics and Molecular Biology | 15 | 14% |
Psychology | 9 | 8% |
Nursing and Health Professions | 7 | 6% |
Agricultural and Biological Sciences | 5 | 5% |
Other | 12 | 11% |
Unknown | 42 | 38% |