A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium

• Type of Material: Article
• Authors: Raquel E. Gur, University of Pennsylvania; Anne S. Bassett, Toronto General Hospital; DM McDonald-McGinn, University of Pennsylvania; CE Bearden, University of California Los Angeles; E Chow, Toronto General Hospital; BS Emanuel, University of Pennsylvania; M Owen, Cardiff University; A Swillen, Katholieke University Leuven; M Van den Bree, Cardiff University; J Vermeesch, Katholieke University Leuven; JAS Vorstman, University Medical Center Utrecht; Stephen Warren, Emory University; T Lehner, National Institute of Mental Health; B Morrow, Albert Einstein College of Medicine
• Language: English
• Date: 2017-12-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 The Author(s).
• Final Published Version (URL): http://dx.doi.org/10.1038/mp.2017.161
• Title of Journal or Parent Work: Molecular Psychiatry
• ISSN: 1359-4184
• Volume: 22
• Issue: 12
• Start Page: 1664
• End Page: 1672
• Grant/Funding Information: The IBBC is supported by the National Institute of Mental Health grants USA U01MH101719, U01MH0101720, CAN+: U01MH0101723, EUA: U01MH101722, EUB: U01MH101724.; Additional support includes: NIH R01MH087626 (REG), R01MH087636 (BSE, DMM-M), R01MH085953 (CEB), Simons Foundation Explorer Award (CEB), RO1MH064824 (WRK), P01HD070454 (BEM, BSE, DMM-M), R01MH107018 (TJS), NIH U54 HD079125 MIND Institute Intellectual and Developmental Disabilities Research Center (TJS), the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities, National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454, RW Woodruff Fund (JFC, OYO), the Canadian Institutes of Health Research (ASB, EWCC, MOP-74631, MOP-97800; ASB, MOP-111238), the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders (ASB), Brain Canada Mental Health Training Award (NJB), Baily Thomas Charitable Trust (2315/1) (MvdB), The Waterloo Foundation (WF918-1234) (MvdB), Wellcome Trust ISSF grant (MvdB), A Medical Research Council (UK) Centre grant G0800509 (MO), CIBERSAM (CA), the Binational Science Foundation, grant number 2011378 (DG), FONDECYT-Chile #1130392 and 1171014 (GMR), Wellcome Trust 110222/Z/15/Z (MN), The FWO grant G.0E11.17 N (JRV), the Brain and Behavior Research Foundation 22597 (AW), the Swiss National Science Foundation (324730_144260) (SE), the EU IMI initiative EU AIMS (DM), the Brain and Behavior Research Foundation (JV), the Brain and Behavior Research Foundation 21278 (MA), the NHMRC 1072593 (AL).
• Keywords: COPY-NUMBER VARIATION; Biochemistry & Molecular Biology; Neurosciences; STRUCTURAL VARIATION; Psychiatry; RISK; Life Sciences & Biomedicine; PSYCHIATRIC-DISORDERS; CONGENITAL HEART-DEFECTS; FUNCTIONAL IMPACT; INTERRATER RELIABILITY; CARDIO-FACIAL-SYNDROME; PRODROMAL SYNDROMES; Science & Technology; Neurosciences & Neurology; PSYCHOSIS-SPECTRUM
• Research Categories: Psychology, Cognitive; Biology, Neuroscience; Psychology, Clinical

Abstract

Rare copy number variants contribute significantly to the risk for schizophrenia, with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2 deletion syndrome (22q11DS) have an estimated 25-fold increased risk for schizophrenia spectrum disorders, compared to individuals in the general population. The International 22q11DS Brain Behavior Consortium is examining this highly informative neurogenetic syndrome phenotypically and genomically. Here we detail the procedures of the effort to characterize the neuropsychiatric and neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and subthreshold expression of psychosis. The genomic approach includes a combination of whole-genome sequencing and genome-wide microarray technologies, allowing the investigation of all possible DNA variation and gene pathways influencing the schizophrenia-relevant phenotypic expression. A phenotypically rich data set provides a psychiatrically well-characterized sample of unprecedented size (n=1616) that informs the neurobehavioral developmental course of 22q11DS. This combined set of phenotypic and genomic data will enable hypothesis testing to elucidate the mechanisms underlying the pathogenesis of schizophrenia spectrum disorders.