Evidence map›Paper›PMID 35449297›Full record

ArticleMolecular psychiatry2022

Integrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder.

Thomas S Wingo, Ekaterina S Gerasimov, Yue Liu, Duc M Duong, Selina M Vattathil, Adriana Lori, Jake Gockley, Michael S Breen, Adam X Maihofer, Caroline M Nievergelt and 9 more

Open access · greenAbstract read
In one paragraph

Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Integrative Transcriptomics and Machine Learning NominateInternational journal of molecular sciences · 2026
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  16. Identifying novel proteins for suicide attempt by integrating proteomes from brain and blood with genome-wide association data.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
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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

19 authors at 8 institutions in 1 country.

Thomas S WingoDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-7679-6282
Ekaterina S GerasimovDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Yue LiuDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Duc M DuongDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Selina M VattathilDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Adriana LoriDepartment of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-8686-0148
Jake GockleySage Bionetworks, Seattle, WA, USA.
Michael S BreenDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adam X MaihoferDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5766-8923
Karestan C KoenenDepartment of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Daniel F LeveyDepartment of Psychiatry Yale, University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-8431-9569
Joel GelernterDepartment of Psychiatry Yale, University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4067-1859
Murray B SteinDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9564-2871
Kerry J ResslerMcLean Hospital, Harvard Medical School, Belmont, MA, USA.ORCID http://orcid.org/0000-0002-5158-1103
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Allan I LeveyDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-3153-502X
Nicholas T SeyfriedDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-4507-624X
Aliza P WingoDepartment of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA. aliza.wingo@emory.edu.ORCID http://orcid.org/0000-0002-6360-6726
Emory University · USUniversity of California San Diego · USYale University · USBroad Institute · USHarvard University · USIcahn School of Medicine at Mount Sinai · USRush University Medical Center · USSage Bionetworks · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
The Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI Amy D Rodriguez · 2020 to 2026
$29.0M
The Emory Alzheimer's Disease CenterP50AG025688 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2005 to 2019
$25.7M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Supplement to AMP-AD Brain Proteomic Network Enhancement, Validation and Translation into CSF BiomarkersU01AG061357 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I, SEYFRIED, NICHOLAS THOMAS · 2018 to 2022
$9.1M
Discovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4M
Psychiatric Genomics Consortium for PTSDR01MH106595 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARESTAN C KOENEN, Caroline M Nievergelt · 2016 to 2026
$8.4M
BLRD VA I01 BX003853BLRD VA I01 BX005686BLRD VA IK4 BX005219NCATS NIH HHS UL1 TR001863NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG072975NIA NIH HHS P50 AG025688NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG053960NIA NIH HHS R01 AG056533NIA NIH HHS R01 AG057911NIA NIH HHS R01 AG061800NIA NIH HHS R01 AG072120NIA NIH HHS R01 AG075827NIA NIH HHS R56 AG060757NIA NIH HHS R56 AG062256NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG057470NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG061357NIMH NIH HHS R01 MH106595NIMH NIH HHS U01 MH115484
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) have identified several risk loci for post-traumatic stress disorder (PTSD); however, how they confer PTSD risk remains unclear. We aimed to identify genes that confer PTSD risk through their effects on brain protein abundance to provide new insights into PTSD pathogenesis. To that end, we integrated human brain proteomes with PTSD GWAS results to perform a proteome-wide association study (PWAS) of PTSD, followed by Mendelian randomization, using a discovery and confirmatory study design. Brain proteomes (N = 525) were profiled from the dorsolateral prefrontal cortex using mass spectrometry. The Million Veteran Program (MVP) PTSD GWAS (n = 186,689) was used for the discovery PWAS, and the Psychiatric Genomics Consortium PTSD GWAS (n = 174,659) was used for the confirmatory PWAS. To understand whether genes identified at the protein-level were also evident at the transcript-level, we performed a transcriptome-wide association study (TWAS) using human brain transcriptomes (N = 888) and the MVP PTSD GWAS results. We identified 11 genes that contribute to PTSD pathogenesis via their respective cis-regulated brain protein abundance. Seven of 11 genes (64%) replicated in the confirmatory PWAS and 4 of 11 also had their cis-regulated brain mRNA levels associated with PTSD. High confidence level was assigned to 9 of 11 genes after considering evidence from the confirmatory PWAS and TWAS. Most of the identified genes are expressed in other PTSD-relevant brain regions and several are preferentially expressed in excitatory neurons, astrocytes, and oligodendrocyte precursor cells. These genes are novel, promising targets for mechanistic and therapeutic studies to find new treatments for PTSD.

Indexed as

Stress Disorders, Post-TraumaticVeteransBrainGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideProteomeTranscriptomeProteome

Identifiers

PMID35449297
PMCPMC9233006
OpenAlexW4224241448

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.