Cited by 58Genomic variations and chromosomal abnormalitiesSchizophrenia research and treatmentGenetics and Neurodevelopmental Disorders

The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia

Open access
Nehme, Ralda, Pietiläinen, Olli, Artomov, Mykyta, Tegtmeyer, Matthew, Valakh, Vera, Lehtonen, Leevi, Bell, Christina, Singh, Tarjinder +37 more·2022·Nature Communications

Published version of a preprint

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-022-31436-8

Cites

123 of 123 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Nehme, R., Pietiläinen, O., Artomov, M., Tegtmeyer, M., Valakh, V., Lehtonen, L., Bell, C., Singh, T., Trehan, A., Sherwood, J., Manning, D., Peirent, E., Malik, R., Guss, E. J., Hawes, D., Beccard, A., Bara, A. M., Hazelbaker, D. Z., Zuccaro, E., Genovese, G., Loboda, A. A., Neumann, A., Lilliehook, C., Kuismin, O., Hamalainen, E., Kurki, M., Hultman, C. M., Kähler, A. K., Paulo, J. A., Ganna, A., Madison, J., Cohen, B., McPhie, D., Adolfsson, R., Perlis, R., Dolmetsch, R., Farhi, S., McCarroll, S., Hyman, S., Neale, B., Barrett, L. E., Harper, W., Palotie, A., Daly, M., & Eggan, K.
Affiliations
  • Broad Institute (US)
  • University of Helsinki (FI)
  • Harvard University (US)
  • Oulu University Hospital (FI)
  • Karolinska Institutet (SE)
  • McLean Hospital (US)
  • Umeå University (SE)
  • Massachusetts General Hospital (US)
Corresponding author
  • Nehme, Ralda
  • Pietiläinen, Olli
  • Eggan, Kevin
Venue
Nature Communications
Published
2022-06-27
Volume
13
Issue
1
Pages
3690-3690
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4283705147
Cited by
58
References
123
Citations by year
2026: 9 · 2025: 18 · 2024: 10 · 2023: 15 · 2022: 6
FWCI
7.39
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
  • DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (U01MH105669)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
22q11.2 deletion syndrome, schizophrenia, presynaptic proteins, induced pluripotent stem cells, CRISPR/Cas9 gene deletion, neural progenitor cells, excitatory neurons, transcriptome, neurodevelopmental disorders, autism spectrum disorder, protein-protein interaction network, proteasome
MeSH terms
Cell Line, DiGeorge Syndrome, Humans, Neurons, RNA, Schizophrenia, Induced Pluripotent Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review