ArticleNature communications2022
The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia.
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Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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34citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% of its field
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.Journal of neurodevelopmental disorders · 2025Pooled it
- Genome-wide tandem repeat expansions modify schizophrenia risk in the presence of a 22q11.2 deletion.Molecular psychiatry · 2026Article
- Gene dosage effects of 22q11.2 copy number variants on in-vivo measures of white matter axonal density and dispersion.Molecular psychiatry · 2026Article
- Developmentally dynamic, non-convergent transcriptomic profiles in CNV models for schizophrenia risk.Molecular psychiatry · 2026Article
- Functional impact of genetic background on variable expressivity in neurodevelopmental disorders.Nature communications · 2026Article
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8.Nucleic acids research · 2026Article
- The systemic effects of 22q11.2 deletion syndrome on immunity.Journal of human immunity · 2026Review
- Minoxidil restores thymic growth in 22q11.2 deletion syndrome by limiting Sox9Journal of human immunity · 2025Article
- Aberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome-associated schizophrenia.Nature communications · 2025Article
- Causal associations between schizophrenia and other psychiatric disorders: A Mendelian randomization study.The Journal of international medical research · 2025Article
- An integrated framework for functional dissection of variable expressivity in genetic disorders.medRxiv : the preprint server for health sciences · 2025Article
- Psychiatric disorders converge on common pathways but diverge in cellular context, spatial distribution, and directionality of genetic effects.medRxiv : the preprint server for health sciences · 2025Article
- Combining phenomics with transcriptomics reveals cell-type-specific morphological and molecular signatures of the 22q11.2 deletion.Nature communications · 2025Article
- Atlas of Proteomic signatures of brain structure and its links to brain disorders.Nature communications · 2025Article
- DGCR8 haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects.Nucleic acids research · 2025Article
- Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications.Molecular psychiatry · 2025Article
- Treatment-resistant schizophrenia with 22q11.2 deletion and additional genetic defects.Neuropsychopharmacology reports · 2024Article
- Schizophrenia genomics: genetic complexity and functional insights.Nature reviews. Neuroscience · 2024Review
- Effects of antipsychotic drugs on energy metabolism.European archives of psychiatry and clinical neuroscience · 2024Article
Corrections and comments
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Authors and funding
45 authors at 9 institutions in 4 countries.
Ralda Nehme *Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. rnehme@broadinstitute.org.ORCID http://orcid.org/0000-0001-7215-3311
Olli Pietiläinen *Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. ollip@broadinstitute.org.ORCID http://orcid.org/0000-0003-4387-1861
Mykyta ArtomovStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-5282-8764
Matthew TegtmeyerStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Vera ValakhStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Leevi LehtonenInstitute for Molecular Medicine Finland, University of Helsinki, FI-00014, Helsinki, Finland.
Christina BellDepartment of Cell Biology, Blavatnik Institute of Harvard Medical School, Boston, MA, USA.
Tarjinder SinghStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-0601-6815
Aditi TrehanStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
John SherwoodStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Danielle ManningStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Emily PeirentStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-3226-7127
Rhea MalikDepartment of Stem Cell and Regenerative Biology, and the Harvard Institute for Stem Cell Biology, Harvard University, Cambridge, MA, 02138, USA.
Ellen J GussDepartment of Stem Cell and Regenerative Biology, and the Harvard Institute for Stem Cell Biology, Harvard University, Cambridge, MA, 02138, USA.ORCID http://orcid.org/0000-0002-2579-8712
Derek HawesStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Amanda BeccardStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Anne M BaraStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Dane Z HazelbakerStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Emanuela ZuccaroDepartment of Stem Cell and Regenerative Biology, and the Harvard Institute for Stem Cell Biology, Harvard University, Cambridge, MA, 02138, USA.
Giulio GenoveseStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-3066-5575
Alexander A LobodaStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Anna NeumannStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-7115-8305
Christina LilliehookStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Outi KuisminPsychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Eija HamalainenInstitute for Molecular Medicine Finland, University of Helsinki, FI-00014, Helsinki, Finland.
Mitja KurkiStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Christina M HultmanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Anna K KählerDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Joao A PauloDepartment of Cell Biology, Blavatnik Institute of Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4291-413X
Andrea GannaStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-8147-240X
Jon MadisonStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Bruce CohenDepartment of Psychiatry, McLean Hospital, Belmont, MA, 02478, USA.ORCID http://orcid.org/0000-0002-8861-6285
Donna McPhieDepartment of Psychiatry, McLean Hospital, Belmont, MA, 02478, USA.
Rolf AdolfssonUmea University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry, 901 85, Umea, Sweden.
Roy PerlisPsychiatry Dept., Massachusetts General Hospital, Boston, MA, 02114, USA.
Ricardo DolmetschNovartis Institutes for Biomedical Research, Novartis, Cambridge, MA, 02139, USA.
Samouil FarhiStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-1359-4568
Steven McCarrollStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Steven HymanStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Ben NealeStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-1513-6077
Lindy E BarrettStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-3229-4774
Wade HarperDepartment of Cell Biology, Blavatnik Institute of Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6944-7236
Aarno PalotieStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-2527-5874
Mark DalyStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-0949-8752
Kevin EgganStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. kevin.eggan@bmrn.com.ORCID http://orcid.org/0000-0003-4436-8467
Broad Institute · USHarvard University · USKarolinska Institutet · SEMcLean Hospital · USUniversity of Helsinki · FIMassachusetts General Hospital · USNovartis (United States) · USOulu University Hospital · FIUmeå University · SE
Funding
Genetic neuroscience: How human genes and alleles shape neuronal phenotypesU01MH115727 · NIMH · BROAD INSTITUTE, INC. · PI ARLOTTA, PAOLA, BABADI, MEHRTASH · 2017 to 2021
$20.8M3/3-Identifying regulatory mutations that influence neuropsychiatric diseaseU01MH105669 · NIMH · BROAD INSTITUTE, INC. · PI DALY, MARK JOSEPH · 2014 to 2018
$4.5MSystematic discovery and functional analysis of the PARKIN modified proteomeR37NS083524 · NINDS · HARVARD MEDICAL SCHOOL · PI HARPER, JEFFREY W · 2013 to 2019
$3.0MAdvancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7MNIGMS NIH HHS R01 GM132129NIMH NIH HHS U01 MH105669NIMH NIH HHS U01 MH115727NINDS NIH HHS R37 NS083524
Abstract
It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.
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DiGeorge SyndromeInduced Pluripotent Stem CellsSchizophreniaCell LineHumansNeuronsRNARNA
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