Evidence map›Paper›PMID 37207277›Full record

ArticleiScience2023

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia.

Yu-Han H Hsu, Greta Pintacuda, Ruize Liu, Eugeniu Nacu, April Kim, Kalliopi Tsafou, Natalie Petrossian, William Crotty, Jung Min Suh, Jackson Riseman and 21 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 1 institution in 2 countries.

Yu-Han H HsuStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Greta PintacudaStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ruize LiuStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Eugeniu NacuStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
April KimStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kalliopi TsafouStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Natalie PetrossianStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
William CrottyStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jung Min SuhStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jackson RisemanStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jacqueline M MartinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Julia C BiaginiStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daya MenaStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joshua K T ChingStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Edyta MalolepszaGenomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Taibo LiStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tarjinder SinghStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tian GeStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Shawn B EgriProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Benjamin TanenbaumProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Caroline R StancliftProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Annie M ApffelProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Stanley Global Asia Initiatives
Steven A CarrProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Monica SchenoneProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jake JaffeProteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nadine FornelosStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Hailiang HuangStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kevin C EgganStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kasper LageStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Broad Institute · US

Funding

Preclinical CoreP50HD103573 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GABRIEL S DICHTER · 2020 to 2026
$9.7M
Systematic Functional Interpretation of Regulatory Variants in SchizophreniaR01MH106575 · NIMH · ENDEAVOR HEALTH CLINICAL OPERATIONS · PI DUAN, JUBAO · 2016 to 2025
$6.1M
Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
Integrating epigenomics with DNA breathing dynamics for human non-coding disease variantsR01MH116281 · NIMH · ENDEAVOR HEALTH CLINICAL OPERATIONS · PI ALEXANDROV, BOIAN STOIANOV, DUAN, JUBAO · 2019 to 2023
$3.0M
2/3 Building Integrative CNS Networks for Genomic Analysis of AutismR01MH109903 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI HANSEN, KASPER LAGE · 2016 to 2020
$1.4M
Harvard Training Program in Bioinformatics Applied to Diabetes, Obesity and Metabolism.T32DK110919 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FLOREZ, JOSE CARLOS, PATEL, CHIRAG J. · 2017 to 2021
$1.3M
From genetic risk variants to convergent protein networks: an integrative approach to elucidate the causal molecular mechanisms of schizophrenia.U01MH121499 · NIMH · BROAD INSTITUTE, INC. · PI HANSEN, KASPER LAGE · 2020 to 2020
$829k
NICHD NIH HHS P50 HD103573NIDDK NIH HHS T32 DK110919NIDDK NIH HHS U01 DK078616NIMH NIH HHS R01 MH106575NIMH NIH HHS R01 MH109903NIMH NIH HHS R01 MH116281NIMH NIH HHS U01 MH121499
6 · The paper itself

Abstract

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Indexed as

Cellular neuroscienceDevelopmental neuroscienceMolecular interactionProteomics

Identifiers

PMID37207277
PMCPMC10189495
OpenAlexW4366256732

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.