Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome
Identifieur interne : 000472 ( Main/Exploration ); précédent : 000471; suivant : 000473Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome
Auteurs : Daniele Merico ; Mehdi Zarrei ; Gregory Costain [Canada] ; Lucas Ogura [Canada] ; Babak Alipanahi [Canada] ; Matthew J. Gazzellone ; Nancy J. Butcher [Canada] ; Bhooma Thiruvahindrapuram ; Thomas Nalpathamkalam ; Eva W. C. Chow [Canada] ; Danielle M. Andrade [Canada] ; Brendan J. Frey [Canada] ; Christian R. Marshall ; Stephen W. Scherer [Canada] ; Anne S. Bassett [Canada]Source :
- G3: Genes|Genomes|Genetics [ 2160-1836 ] ; 2015.
Abstract
Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of
Url:
DOI: 10.1534/g3.115.021345
PubMed: 26384369
PubMed Central: 4632064
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome</title><author><name sortKey="Merico, Daniele" sort="Merico, Daniele" uniqKey="Merico D" first="Daniele" last="Merico">Daniele Merico</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Zarrei, Mehdi" sort="Zarrei, Mehdi" uniqKey="Zarrei M" first="Mehdi" last="Zarrei">Mehdi Zarrei</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Costain, Gregory" sort="Costain, Gregory" uniqKey="Costain G" first="Gregory" last="Costain">Gregory Costain</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Medical Genetics Residency Training Program, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Medical Genetics Residency Training Program, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Ogura, Lucas" sort="Ogura, Lucas" uniqKey="Ogura L" first="Lucas" last="Ogura">Lucas Ogura</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Alipanahi, Babak" sort="Alipanahi, Babak" uniqKey="Alipanahi B" first="Babak" last="Alipanahi">Babak Alipanahi</name><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Electrical and Computer Engineering, University of Toronto, Ontario, M5S 2E4 Canada, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Gazzellone, Matthew J" sort="Gazzellone, Matthew J" uniqKey="Gazzellone M" first="Matthew J." last="Gazzellone">Matthew J. Gazzellone</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Butcher, Nancy J" sort="Butcher, Nancy J" uniqKey="Butcher N" first="Nancy J." last="Butcher">Nancy J. Butcher</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Thiruvahindrapuram, Bhooma" sort="Thiruvahindrapuram, Bhooma" uniqKey="Thiruvahindrapuram B" first="Bhooma" last="Thiruvahindrapuram">Bhooma Thiruvahindrapuram</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Nalpathamkalam, Thomas" sort="Nalpathamkalam, Thomas" uniqKey="Nalpathamkalam T" first="Thomas" last="Nalpathamkalam">Thomas Nalpathamkalam</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Chow, Eva W C" sort="Chow, Eva W C" uniqKey="Chow E" first="Eva W. C." last="Chow">Eva W. C. Chow</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Andrade, Danielle M" sort="Andrade, Danielle M" uniqKey="Andrade D" first="Danielle M." last="Andrade">Danielle M. Andrade</name><affiliation wicri:level="4"><nlm:aff id="aff6">Division of Neurology, Department of Medicine, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation><nlm:aff id="aff7">Epilepsy Genetics Program, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Ontario, M5T 2S8 Canada</nlm:aff><wicri:noCountry code="subfield">M5T 2S8 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Frey, Brendan J" sort="Frey, Brendan J" uniqKey="Frey B" first="Brendan J." last="Frey">Brendan J. Frey</name><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Electrical and Computer Engineering, University of Toronto, Ontario, M5S 2E4 Canada, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Marshall, Christian R" sort="Marshall, Christian R" uniqKey="Marshall C" first="Christian R." last="Marshall">Christian R. Marshall</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Scherer, Stephen W" sort="Scherer, Stephen W" uniqKey="Scherer S" first="Stephen W." last="Scherer">Stephen W. Scherer</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8">McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S." last="Bassett">Anne S. Bassett</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9">Department of Psychiatry, and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry, and Toronto General Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation><nlm:aff id="aff10">Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5S 2S1 Canada</nlm:aff><wicri:noCountry code="subfield">M5S 2S1 Canada</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff11">The Dalglish Family Hearts and Minds Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 2C4 Canada</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26384369</idno><idno 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xml:lang="en" level="a" type="main">Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome</title><author><name sortKey="Merico, Daniele" sort="Merico, Daniele" uniqKey="Merico D" first="Daniele" last="Merico">Daniele Merico</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Zarrei, Mehdi" sort="Zarrei, Mehdi" uniqKey="Zarrei M" first="Mehdi" last="Zarrei">Mehdi Zarrei</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Costain, Gregory" sort="Costain, Gregory" uniqKey="Costain G" first="Gregory" last="Costain">Gregory Costain</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Medical Genetics Residency Training Program, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Medical Genetics Residency Training Program, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Ogura, Lucas" sort="Ogura, Lucas" uniqKey="Ogura L" first="Lucas" last="Ogura">Lucas Ogura</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Alipanahi, Babak" sort="Alipanahi, Babak" uniqKey="Alipanahi B" first="Babak" last="Alipanahi">Babak Alipanahi</name><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Electrical and Computer Engineering, University of Toronto, Ontario, M5S 2E4 Canada, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Gazzellone, Matthew J" sort="Gazzellone, Matthew J" uniqKey="Gazzellone M" first="Matthew J." last="Gazzellone">Matthew J. Gazzellone</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Butcher, Nancy J" sort="Butcher, Nancy J" uniqKey="Butcher N" first="Nancy J." last="Butcher">Nancy J. Butcher</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Thiruvahindrapuram, Bhooma" sort="Thiruvahindrapuram, Bhooma" uniqKey="Thiruvahindrapuram B" first="Bhooma" last="Thiruvahindrapuram">Bhooma Thiruvahindrapuram</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Nalpathamkalam, Thomas" sort="Nalpathamkalam, Thomas" uniqKey="Nalpathamkalam T" first="Thomas" last="Nalpathamkalam">Thomas Nalpathamkalam</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Chow, Eva W C" sort="Chow, Eva W C" uniqKey="Chow E" first="Eva W. C." last="Chow">Eva W. C. Chow</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Andrade, Danielle M" sort="Andrade, Danielle M" uniqKey="Andrade D" first="Danielle M." last="Andrade">Danielle M. Andrade</name><affiliation wicri:level="4"><nlm:aff id="aff6">Division of Neurology, Department of Medicine, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, University of Toronto, Ontario, M5S 1A8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation><nlm:aff id="aff7">Epilepsy Genetics Program, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Ontario, M5T 2S8 Canada</nlm:aff><wicri:noCountry code="subfield">M5T 2S8 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Frey, Brendan J" sort="Frey, Brendan J" uniqKey="Frey B" first="Brendan J." last="Frey">Brendan J. Frey</name><affiliation wicri:level="4"><nlm:aff id="aff4">Department of Electrical and Computer Engineering, University of Toronto, Ontario, M5S 2E4 Canada, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Marshall, Christian R" sort="Marshall, Christian R" uniqKey="Marshall C" first="Christian R." last="Marshall">Christian R. Marshall</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Scherer, Stephen W" sort="Scherer, Stephen W" uniqKey="Scherer S" first="Stephen W." last="Scherer">Stephen W. Scherer</name><affiliation><nlm:aff id="aff1">The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 0A4 Canada</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8">McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 0A4 Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S." last="Bassett">Anne S. Bassett</name><affiliation wicri:level="1"><nlm:aff id="aff2">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry University of Toronto, Ontario, M5T 1R8 Canada, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9">Department of Psychiatry, and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Psychiatry, and Toronto General Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation><nlm:aff id="aff10">Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5S 2S1 Canada</nlm:aff><wicri:noCountry code="subfield">M5S 2S1 Canada</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff11">The Dalglish Family Hearts and Minds Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada</nlm:aff><wicri:noCountry code="subfield">M5G 2C4 Canada</wicri:noCountry></affiliation></author></analytic><series><title level="j">G3: Genes|Genomes|Genetics</title><idno type="eISSN">2160-1836</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of <italic>DGCR8</italic> haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age >50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal <italic>P</italic> = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a <italic>DGCR8</italic> mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal <italic>P</italic> = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Andrade, D M" uniqKey="Andrade D">D. M. Andrade</name></author><author><name sortKey="Krings, T" uniqKey="Krings T">T. Krings</name></author><author><name sortKey="Chow, E W" uniqKey="Chow E">E. W. Chow</name></author><author><name sortKey="Kiehl, T R" uniqKey="Kiehl T">T. R. Kiehl</name></author><author><name sortKey="Bassett, A S" uniqKey="Bassett A">A. S. 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Andrade</name><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S." last="Bassett">Anne S. Bassett</name><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S." last="Bassett">Anne S. Bassett</name><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S." last="Bassett">Anne S. Bassett</name><name sortKey="Butcher, Nancy J" sort="Butcher, Nancy J" uniqKey="Butcher N" first="Nancy J." last="Butcher">Nancy J. Butcher</name><name sortKey="Chow, Eva W C" sort="Chow, Eva W C" uniqKey="Chow E" first="Eva W. C." last="Chow">Eva W. C. Chow</name><name sortKey="Chow, Eva W C" sort="Chow, Eva W C" uniqKey="Chow E" first="Eva W. C." last="Chow">Eva W. C. Chow</name><name sortKey="Costain, Gregory" sort="Costain, Gregory" uniqKey="Costain G" first="Gregory" last="Costain">Gregory Costain</name><name sortKey="Frey, Brendan J" sort="Frey, Brendan J" uniqKey="Frey B" first="Brendan J." last="Frey">Brendan J. Frey</name><name sortKey="Ogura, Lucas" sort="Ogura, Lucas" uniqKey="Ogura L" first="Lucas" last="Ogura">Lucas Ogura</name><name sortKey="Scherer, Stephen W" sort="Scherer, Stephen W" uniqKey="Scherer S" first="Stephen W." last="Scherer">Stephen W. Scherer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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