Evidence map›Paper›PMID 39043921›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2024

Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits.

Emily E Hartwell, Zeal Jinwala, Jackson Milone, Sarah Ramirez, Joel Gelernter, Henry R Kranzler, Rachel L Kember

Abstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 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.

  1. Article
  2. Review
  3. Article
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  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Emily E HartwellCrescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5137-9714
Zeal JinwalaCrescenz VA Medical Center, Philadelphia, PA, USA.
Jackson MiloneUniversity of Pennsylvania, Philadelphia, PA, USA.
Sarah RamirezUniversity of Pennsylvania, Philadelphia, PA, USA.
Joel GelernterWest Haven VA Medical Center, West Haven, CT, USA.ORCID http://orcid.org/0000-0002-4067-1859
Henry R KranzlerCrescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1018-0450
Rachel L KemberCrescenz VA Medical Center, Philadelphia, PA, USA. rkember@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0001-8820-2659

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
Methamphetamine and Other Substance Use Disorder Genetics in ThailandR01DA037974 · NIDA · YALE UNIVERSITY · PI JOEL GELERNTER, Marc N Potenza · 2015 to 2026
$6.7M
Genetic Basis of the Risk and Consequences of Cannabis Exposure in HumansR01DA058862 · NIDA · YALE UNIVERSITY · PI DEEPAK Cyril D'SOUZA, JOEL GELERNTER · 2023 to 2026
$2.6M
Characterizing the phenotypic spectrum associated with genetic liability for alcohol use disorderK01AA028292 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI KEMBER, RACHEL LORRAINE · 2021 to 2024
$505k
Genetic Vulnerability for Sustained Multi-Substance Use in MVPI01BX004820 · VA · VA CONNECTICUT HEALTHCARE SYSTEM · PI Amy Caroline Justice, HENRY RICHARD KRANZLER · 2020 to 2026
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Genetic architecture of substance use disorders and major depressionIK2CX002336 · VA · PHILADELPHIA VA MEDICAL CENTER · PI Emily Hartwell · 2022 to 2026
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BLRD VA I01 BX004820CSRD VA IK2 CX002336NCATS NIH HHS UL1 TR001863NIAAA NIH HHS K01 AA028292NIDA NIH HHS R01 DA058862U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) K01AA028292U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R01DA037974U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R01DA058862U.S. Department of Veterans Affairs (Department of Veterans Affairs) VISN1 MIRECCU.S. Department of Veterans Affairs (Department of Veterans Affairs) VISN4 MIRECC
6 · The paper itself

Abstract

Co-occurring psychiatric, medical, and substance use disorders (SUDs) are common, but the complex pathways leading to such comorbidities are poorly understood. A greater understanding of genetic influences on this phenomenon could inform precision medicine efforts. We used the Yale-Penn dataset, a cross-sectional sample enriched for individuals with SUDs, to examine pleiotropic effects of genetic liability for psychiatric and somatic traits. Participants completed an in-depth interview that provides information on demographics, environment, medical illnesses, and psychiatric and SUDs. Polygenic scores (PGS) for psychiatric disorders and somatic traits were calculated in European-ancestry (EUR; n = 5691) participants and, when discovery datasets were available, for African-ancestry (AFR; n = 4918) participants. Phenome-wide association studies (PheWAS) were then conducted. In AFR participants, the only PGS with significant associations was bipolar disorder (BD), all of which were with substance use phenotypes. In EUR participants, PGS for major depressive disorder (MDD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), body mass index (BMI), coronary artery disease (CAD), and type 2 diabetes (T2D) all showed significant associations, the majority of which were with phenotypes in the substance use categories. For instance, PGS

Indexed as

Genetic PleiotropyMental DisordersMultifactorial InheritancePhenotypeSubstance-Related DisordersAdultAfrican PeopleComorbidityCross-Sectional StudiesFemaleGenome-Wide Association StudyHumansMaleMiddle AgedWhite People

Identifiers

PMID39043921
PMCPMC11480112

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.