Evidence map›Paper›PMID 30340753›Full record

ArticleBiological psychiatry2019

A Longitudinal Model of Human Neuronal Differentiation for Functional Investigation of Schizophrenia Polygenic Risk.

Anil P S Ori, Merel H M Bot, Remco T Molenhuis, Loes M Olde Loohuis, Roel A Ophoff

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Fibroblasts as an in vitro model of circadian genetic and genomic studies.Mammalian genome : official journal of the International Mammalian Genome Society · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Anil P S OriCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
Merel H M BotCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
Remco T MolenhuisCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
Loes M Olde LoohuisCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
Roel A OphoffCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: ophoff@ucla.edu.
University of California, Los Angeles · US

Funding

1/2 Genomic Strategies to Identify High-impact Psychiatric Risk VariantsU01MH105578 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B., GESCHWIND, DANIEL H · 2014 to 2018
$8.5M
Genomic Studies of Bipolar Disorder in a Large Cohort from The NetherlandsR01MH090553 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OPHOFF, ROEL A · 2010 to 2014
$6.0M
NIMH NIH HHS R01 MH090553NIMH NIH HHS U01 MH105578
6 · The paper itself

Abstract

backgroundCommon psychiatric disorders are characterized by complex disease architectures with many small genetic effects that contribute and complicate biological understanding of their etiology. There is therefore a pressing need for in vitro experimental systems that allow for interrogation of polygenic psychiatric disease risk to study the underlying biological mechanisms.

methodsWe have developed an analytical framework that integrates genome-wide disease risk from genome-wide association studies with longitudinal in vitro gene expression profiles of human neuronal differentiation.

resultsWe demonstrate that the cumulative impact of risk loci of specific psychiatric disorders is significantly associated with genes that are differentially expressed and upregulated during differentiation. We find the strongest evidence for schizophrenia, a finding that we replicate in an independent dataset. A longitudinal gene cluster involved in synaptic function primarily drives the association with schizophrenia risk.

conclusionsThese findings reveal that in vitro human neuronal differentiation can be used to translate the polygenic architecture of schizophrenia to biologically relevant pathways that can be modeled in an experimental system. Overall, this work emphasizes the use of longitudinal in vitro transcriptomic signatures as a cellular readout and the application to the genetics of complex traits.

Indexed as

Cell DifferentiationGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyModels, NeurologicalMultifactorial InheritanceNeural Stem CellsHumansLongitudinal StudiesRiskSchizophreniaGenome-wide disease riskNeuronal stem cellsPolygenicityPsychiatric disordersSchizophreniaSynaptic function

Identifiers

PMID30340753
PMCPMC6401362
OpenAlexW2950033711

What OpenQuestion holds

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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.