Evidence map›Paper›PMID 32792264›Full record

ReviewBiological psychiatry2021

Transcriptomic Insight Into the Polygenic Mechanisms Underlying Psychiatric Disorders.

Leanna M Hernandez, Minsoo Kim, Gil D Hoftman, Jillian R Haney, Luis de la Torre-Ubieta, Bogdan Pasaniuc, Michael J Gandal

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Biological psychiatry, 2021. 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.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 3% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

7 authors at 1 institution in 1 country.

Leanna M HernandezDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Minsoo KimDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, 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.
Gil D HoftmanDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Jillian R HaneyDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Luis de la Torre-UbietaDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Bogdan PasaniucProgram in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, 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; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Michael J GandalDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, 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: mgandal@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
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
Population-level and mechanistic dissection of 17q21 structural variant association with psychiatric traitsR01MH123922 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.1M
Neurodevelopment and Psychosis in the 22q11.2 Copy Number VariantsR37MH085953 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARRIE E BEARDEN · 2023 to 2026
$2.9M
Training Grant in Neurobehavioral GeneticsT32MH073526 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, GESCHWIND, DANIEL H · 2006 to 2020
$2.4M
Integrative approaches for mapping the genetic risk of complex traitsR01HG009120 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PASANIUC, BOGDAN · 2017 to 2021
$2.3M
Gene-brain-environment interactions as determinants of typical and atypical developmental trajectoriesK00MH119663 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHARMA, LEANNA MARIE HERNANDEZ · 2018 to 2021
$325k
NHGRI NIH HHS R01 HG009120NIGMS NIH HHS T32 GM008042NIMH NIH HHS K00 MH119663NIMH NIH HHS R01 MH121521NIMH NIH HHS R01 MH123922NIMH NIH HHS R37 MH085953NIMH NIH HHS T32 MH073526NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

Over the past decade, large-scale genetic studies have successfully identified hundreds of genetic variants robustly associated with risk for psychiatric disorders. However, mechanistic insight and clinical translation continue to lag the pace of risk variant identification, hindered by the sheer number of targets and their predominant noncoding localization, as well as pervasive pleiotropy and incomplete penetrance. Successful next steps require identification of "causal" genetic variants and their proximal biological consequences; placing variants within biologically defined functional contexts, reflecting specific molecular pathways, cell types, circuits, and developmental windows; and characterizing the downstream, convergent neurobiological impact of polygenicity within an individual. Here, we discuss opportunities and challenges of high-throughput transcriptomic profiling in the human brain, and how transcriptomic approaches can help pinpoint mechanisms underlying genetic risk for psychiatric disorders at a scale necessary to tackle daunting levels of polygenicity. These include transcriptome-wide association studies for risk gene prioritization through integration of genome-wide association studies with expression quantitative trait loci. We outline transcriptomic results that inform our understanding of the brain-level molecular pathology of psychiatric disorders, including autism spectrum disorder, bipolar disorder, major depressive disorder, and schizophrenia. Finally, we discuss systems-level approaches for integration of distinct genetic, genomic, and phenotypic levels, including combining spatially resolved gene expression and human neuroimaging maps. Results highlight the importance of understanding gene expression (dys)regulation across human brain development as a major contributor to psychiatric disease pathogenesis, from common variants acting as expression quantitative trait loci to rare variants enriched for gene expression regulatory pathways.

Indexed as

Autism Spectrum DisorderMajor Depressive DisorderGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMultifactorial InheritanceTranscriptomeAutismBrainCoexpressionGenomicsGWASSchizophreniaTranscriptomics

Identifiers

PMID32792264
PMCPMC7718368
OpenAlexW3035248823

What OpenQuestion holds

Textmetadata
LicenceTDM
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.