{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Anne Bassett"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000600"],"host":["EGA"],"description":["EGA DAC EGAC00001000600"],"repository":["EGA"],"email":["anne.bassett@utoronto.ca"],"pubmed_abstract":["Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 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 P = 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 DGCR8 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 P = 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."],"pubmed_title":["Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome."],"pubmed_authors":["Merico Daniele D, Zarrei Mehdi M, Costain Gregory G, Ogura Lucas L, Alipanahi Babak B, Gazzellone Matthew J MJ, Butcher Nancy J NJ, Thiruvahindrapuram Bhooma B, Nalpathamkalam Thomas T, Chow Eva W C EW, Andrade Danielle M DM, Frey Brendan J BJ, Marshall Christian R CR, Scherer Stephen W SW, Bassett Anne S AS"],"name_synonyms":["fbwd4, l(2)04454, DmelCG1772, dac, CIB1, shsf3, shfm3, Decapo., E(Sev-CycE)2B, p21[dacapo], Fbw4, FBW4, dactylin, E130112M23Rik, Dach, CDKN2B, cdi4, SHFM3, Dac, DAC, p27[Dap], dactylyn, dacapo/cyclin-dependent kinase interactor 4, AI182278, p21, CG1772, FBWD4, Dap, Cdi4, CDI4, CES5A1, p27, P15, fbw4, SHSF3"],"pubmed_title_synonyms":["Velo Cardio Facial Syndrome, SCHIZO NEC-CHR/EXACERB, Disorders, schizophrenia, Autosomal Dominant Opitz G Bbb Syndrome, 22q11.2, SCHIZO NEC-SUBCHR/EXACER, Modern, DiGeorge Sequence, Conotruncal Anomaly Face Syndrome, Third and Fourth Pharyngeal Pouch Syndrome, Shprintzen VCF Syndrome, unspecified (disorder), Human, Relative, schizophrenia with or without an affective disorder, Schizophrenia NOS, Familial Third and Fourth Pharyngeal Pouch Syndrome, unspecified, Autosomal Dominant Opitz G-Bbb Syndrome, Dementia Praecox, SCHIZO NOS-CHR/EXACERB, Homo sapiens, Other specified types of schizophrenia, Schizophrenic disorders (disorder), SCHIZOPHRENIA NEC-SUBCHR, Relative Risks, chronic state, SCHIZOPHRENIA NEC-CHR, Schizophrenias, unspecified state, VCF Syndrome, Velocardiofacial Syndrome, Shprintzen Syndrome, subchronic state with acute exacerbation, Unspecified schizophrenia, VCF, subchronic state, Sedlackova, 22q11.2DS, Man, Relative Risk, Deletion Syndrome, Velo-Cardio-Facial, Deletion 22q11.2 Syndrome, SCHIZOPHRENIA NEC-UNSPEC, [X]Schizophrenia, Catch22, Schizophrenia (disorder), DiGeorge syndrome, Unspecified schizophrenia (disorder), Man (Taxonomy), DiGeorge sequence, Sedlackova Syndrome, Risk, Genomes, Schizophrenic, DiGeorge, susceptibility to, Risks, Schizophrenic disorders, Shprintzen, Hypoplasia of Thymus and Parathyroids, whole genome, Schizophrenic Disorder, Schizophrenia NOS (disorder), Conotruncal Anomaly Face Syndrome (CTAF), SCZD, Velo-Cardio-Facial Syndrome, DiGeorge Anomaly, schizoaffective disorder, in remission, Schizophrenic Disorders, Disorder, Modern Man, Syndrome, 22q11.2 Deletion Syndrome, Velocardiofacial., chronic state with acute exacerbation, Pharyngeal Pouch Syndrome, SCHIZOPHRENIA NOS-UNSPEC, SCHIZOPHRENIA NEC-REMISS, Thymic Aplasia Syndrome, humans, SCHIZO NOS-SUBCHR/EXACER"],"pubmed_abstract_synonyms":["Networks, Non Protein Coding, joints, Disorders, Schizophreniform Disorders, Materials, nerve fiber, Relative, Noncoding RNA, Personal, unspecified, Dementia Praecox, DmelCG1800, Circuit, Joint, chronic state, Transcriptional Networks, symptoms, unspecified state, Unspecified schizophrenia, Psychological, Transcriptional, SCHIZOPHRENIA NEC-UNSPEC, Unspecified schizophrenia (disorder), Genomes, Non-Protein-Coding RNA, long, neuronal cell projection, Schizophrenic disorders, chromatid, Social, genetic, set, neuron protrusion, geographical area, Non Coding, neurite, Pasha, Gene Network, Behavior Disorder, Social Power, cg1800, Psychotic Disorders, protein-coding, PASHA, Power, SCHIZO NOS-SUBCHR/EXACER, mental process disease, screening, joint, Vo59c07, wide/broad, familial, incomplete, dmDGCR8, Psychoses, Psychological Powers, D16Wis2, CG1800, abolished, Non-Coding RNA, SCHIZOPHRENIA NEC-SUBCHR, RENBP, Relative Risks, Schizophrenias, Genetic Materials, Non-Peptide-Coding, Genetic Material, [X]Schizophrenia, positional polypeptide feature, Gene Circuit, Risk, susceptibility to, signs, whole genome, Nontranslated, Non-Protein-Coding, AGE, Schizophrenic Disorders, Phenotypes, Psychotic, wide, D16H22S788E, Chromosome, Gene Modules, Regulatory Networks, Material, C22orf12, DGCRK6, chronic state with acute exacerbation, Cistron, inherited genetic, PSYCHOTIC DIS, Powers, Brief Reactive Psychoses, mental or behavioral disorder, Mental Disorder, Gruppe, Psychological Power, Schizoaffective Disorders, Modules, Gene Regulatory, Nontranslated RNA, npcRNA, Professional Power, region or site annotation, Psychosis, Gene, Network, broad, unspecified (disorder), schizophrenia with or without an affective disorder, Schizophrenia NOS, SCHIZO NOS-CHR/EXACERB, Other specified types of schizophrenia, mental disorders, Transcriptional Network, Gene Regulatory Network, subchronic state, neuron process, Module, study, pasha, Schizophrenia (disorder), positional, Regulatory Network, Circuits, Schizoaffective Disorder, Genetic, N41, Non-Coding, disease of mental health, Schizophreniform, Schizophrenic Disorder, SCZD, Gy1, schizoaffective disorder, grupos, mental disorder, Disorder, articular joint, SCHIZOPHRENIA NEC-REMISS, D16H22S1742E, constitutitional genetic, Reactive Psychosis, Brief Reactive Psychosis, Psychiatric Disorder, RNA, SCHIZO NEC-CHR/EXACERB, findings, grupo, schizophrenia, Brief Reactive, Non Peptide Coding, RnBP, Brief, SCHIZO NEC-SUBCHR/EXACER, Psychotic Disorder, Phenotypes., GlcNAc 2-epimerase, Haploinsufficiencies, DGCR8, Cistrons, Gene Circuits, group, prophase chromosome, Non-Peptide-Coding RNA, N-acetyl-D-glucosamine 2-epimerase, Schizophrenic disorders (disorder), SCHIZOPHRENIA NEC-CHR, sequence, Professional, rare (European definition), Schizophreniform Disorder, subchronic state with acute exacerbation, Untranslated RNA, Relative Risk, Schizoaffective, articulation, Schizophrenic, ensemble, Gene Module, interphase chromosome, Risks, Rest, INSDC_qualifier:other, Schizophrenia NOS (disorder), primary structure of sequence macromolecule, in remission, Personal Power, DEL, Isolation of Nuclei TAgged in specific Cell Types, Gene Networks, Power (Psychology), renin-binding protein, Noncoding, SCHIZOPHRENIA NOS-UNSPEC, disorder of mental process, Reactive Psychoses, hereditary, groupe, mental or behavioural disorder"],"additional_accession":[]},"is_claimable":false,"name":"DAC for EGAS00001002275","description":"Data Access Committee EGAC00001000600","dates":{"output":"2025-1-9"},"accession":"EGAC00001000600","cross_references":{"TAXONOMY":["9606"],"pubmed":["26384369"],"EGA":["EGAS00001002275","EGAS00001002344","EGAD00001003187"]}}