Evidence map›Paper›PMID 31626773›Full record

ArticleCell2019

Genetic Control of Expression and Splicing in Developing Human Brain Informs Disease Mechanisms.

Rebecca L Walker, Gokul Ramaswami, Christopher Hartl, Nicholas Mancuso, Michael J Gandal, Luis de la Torre-Ubieta, Bogdan Pasaniuc, Jason L Stein, Daniel H Geschwind

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 176 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
176citing papers in PubMed, 4 pooled it
27.9field-weighted citation impact, top 1% 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

176 citing papers in PubMed, 4 syntheses or guidelines pooled it, 300 citations in OpenAlex.

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116 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Rebecca L WalkerDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA; Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gokul RamaswamiDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Christopher HartlDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA; Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nicholas MancusoDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Michael J GandalDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Luis de la Torre-UbietaDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA; Department of Psychiatry, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Bogdan PasaniucDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jason L SteinDepartment of Genetics and UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Daniel H GeschwindDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA; Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu.
Center for Autism and Related Disorders · USUniversity of California, Los Angeles · USUniversity of North Carolina at Chapel Hill · US

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 1991 to 2018
$39.9M
Autism Genetics, Phase II: Increasing Representation of Human DiversityR01MH100027 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2013 to 2024
$31.7M
Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
Identification and Characterization of Asymmetrically-Expressed GenesR37MH060233 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2006 to 2014
$5.3M
2/2-Discovery and validation of neuronal enhancers associated with the development of psychiatric disordersU01MH116489 · NIMH · UNIVERSITY OF CHICAGO · PI GAYNOR, SOPHIA, GESCHWIND, DANIEL H · 2018 to 2022
$4.5M
Isoform-level probabilistic transcriptome-wide association to undercover neurogenetic mechanisms underlying complex psychiatric traitsR01MH121521 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.4M
Epigenetic and Transcriptional Dysregulation in Autism Spectrum DisorderR01MH094714 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2011 to 2015
$2.8M
2/3 Integrative Genomic Analysis of Human Brain Development and AutismR01MH110927 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2016 to 2019
$2.7M
1/3 Building integrative CNS networks for genomic analysis of autismR01MH109912 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2016 to 2020
$2.6M
Genetic Influences on Human Cortical DevelopmentR00MH102357 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STEIN, JASON LOUIS · 2016 to 2018
$747k
Systems level integration of genetic, transcriptomic, and epigenomic data in autismF32MH114620 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAMASWAMI, GOKUL · 2018 to 2019
$111k
NIAID NIH HHS P30 AI028697NIMH NIH HHS F32 MH114620NIMH NIH HHS R00 MH102357NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH100027NIMH NIH HHS R01 MH109912NIMH NIH HHS R01 MH110927NIMH NIH HHS R01 MH121521NIMH NIH HHS R37 MH060233NIMH NIH HHS U01 MH116489NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

Tissue-specific regulatory regions harbor substantial genetic risk for disease. Because brain development is a critical epoch for neuropsychiatric disease susceptibility, we characterized the genetic control of the transcriptome in 201 mid-gestational human brains, identifying 7,962 expression quantitative trait loci (eQTL) and 4,635 spliceQTL (sQTL), including several thousand prenatal-specific regulatory regions. We show that significant genetic liability for neuropsychiatric disease lies within prenatal eQTL and sQTL. Integration of eQTL and sQTL with genome-wide association studies (GWAS) via transcriptome-wide association identified dozens of novel candidate risk genes, highlighting shared and stage-specific mechanisms in schizophrenia (SCZ). Gene network analysis revealed that SCZ and autism spectrum disorder (ASD) affect distinct developmental gene co-expression modules. Yet, in each disorder, common and rare genetic variation converges within modules, which in ASD implicates superficial cortical neurons. More broadly, these data, available as a web browser and our analyses, demonstrate the genetic mechanisms by which developmental events have a widespread influence on adult anatomical and behavioral phenotypes.

Indexed as

Autism Spectrum DisorderBrainFemaleFetusGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseGenome-Wide Association StudyGestational AgeHumansMaleNeuronsPolymorphism, Single NucleotideQuantitative Trait LociRNA SplicingSchizophreniaTranscriptomeautismeQTLgene networksgene regulationhuman cortical developmentschizophreniasplicing regulationsQTLTWAS

Identifiers

PMID31626773
PMCPMC8963725
OpenAlexW2980980552

What OpenQuestion holds

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Registered trials

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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.