Evidence map›Paper›PMID 39433874›Full record

ArticleCommunications biology2024

Analyses of GWAS signal using GRIN identify additional genes contributing to suicidal behavior.

Kyle A Sullivan, Matthew Lane, Mikaela Cashman, J Izaak Miller, Mirko Pavicic, Angelica M Walker, Ashley Cliff, Jonathon Romero, Xuejun Qin, Niamh Mullins and 15 more

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

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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

25 authors.

Kyle A SullivanComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0002-4621-5598
Matthew LaneThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee Knoxville, Knoxville, TN, USA.ORCID 0000-0002-7750-6822
Mikaela CashmanComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
J Izaak MillerComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Mirko PavicicComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0002-2908-3183
Angelica M WalkerThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee Knoxville, Knoxville, TN, USA.
Ashley CliffThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee Knoxville, Knoxville, TN, USA.
Jonathon RomeroThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee Knoxville, Knoxville, TN, USA.
Xuejun QinDurham Veterans Affairs Health Care System, Durham, NC, USA.ORCID 0000-0001-9169-253X
Niamh MullinsDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.ORCID 0000-0001-8021-839X
Anna DochertyDepartment of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.ORCID 0000-0001-7139-7007
Hilary CoonDepartment of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.ORCID 0000-0002-8877-5446
Douglas M RuderferDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-2365-386X
International Suicide Genetics Consortium
VA Million Veteran Program
MVP Suicide Exemplar Workgroup
Michael R GarvinComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA.ORCID 0000-0002-2204-7569
John P PestianComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Allison E Ashley-KochDuke University School of Medicine, Duke University, Durham, NC, USA.ORCID 0000-0001-5409-9155
Jean C BeckhamDurham Veterans Affairs Health Care System, Durham, NC, USA.
Benjamin McMahonTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
David W OslinVISN 4 Mental Illness Research, Education, and Clinical Center, Center of Excellence, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Nathan A KimbrelDurham Veterans Affairs Health Care System, Durham, NC, USA. nathan.kimbrel@va.gov.ORCID 0000-0001-7218-1005
Daniel A JacobsonComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA. jacobsonda@ornl.gov.ORCID 0000-0002-9822-8251
David KainerComputational and Predictive Biology, Oak Ridge National Laboratory, Oak Ridge, TN, USA. d.kainer@uq.edu.au.ORCID 0000-0001-7271-4676

Funding

Synergy Core (SynC)P50DA054071 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI Vanessa Troiani · 2022 to 2026
$13.1M
Gene Network Identification and Integration (GNetii) Approach to Understanding the Biology Underlying HIV and Drug Abuse.R01DA051908 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI JACOBSON, DANIEL A, JOHNSON, ERIC OTTO · 2020 to 2024
$3.4M
Integrating Multiple Omics to Illuminate Gene Networks Underlying Cigarette Smoking and Opioids.R01DA051913 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI HANCOCK, DANA B, JACOBSON, DANIEL A · 2020 to 2024
$2.9M
Distinguishing Clinical and Genetic Risk of Suicidal Ideation from Attempts to Inform PreventionR01MH121455 · NIMH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RUDERFER, DOUGLAS, WALSH, COLIN GEORGE · 2020 to 2024
$2.7M
2/2 Leveraging electronic health records for pharmacogenomics of psychiatric diordersR01MH116269 · NIMH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RUDERFER, DOUGLAS, WALSH, COLIN GEORGE · 2019 to 2022
$1.7M
Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) NARSAD Young Investigator Award No. 29551CSRD VA IK6 CX002767Department of Education and Training | Australian Research Council (ARC) CE200100015NIDA NIH HHS P50 DA054071NIDA NIH HHS R01 DA051908NIDA NIH HHS R01 DA051913NIMH NIH HHS R01 MH116269NIMH NIH HHS R01 MH121455U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH116269U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH121455U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA041913U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA051908
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. We present GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks when GWAS thresholds are relaxed. GRIN was validated on both simulated interrelated gene sets as well as multiple GWAS traits. From multiple GWAS summary statistics of suicide attempt, a complex phenotype, GRIN identified additional genes that replicated across independent cohorts and retained biologically interrelated genes despite a relaxed significance threshold. We present a conceptual model of how these retained genes interact through neurobiological pathways that may influence suicidal behavior, and identify existing drugs associated with these pathways that would not have been identified under traditional GWAS thresholds. We demonstrate GRIN's utility in boosting GWAS results by increasing the number of true positive genes identified from GWAS results.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudySuicideGene Regulatory NetworksHumansPhenotypePolymorphism, Single NucleotideSuicide, Attempted

Identifiers

PMID39433874
PMCPMC11494055

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.