Evidence map›Paper›PMID 38370821›Full record

ArticlebioRxiv : the preprint server for biology2024

Functional 3'-UTR Variants Identify Regulatory Mechanisms Impacting Alcohol Use Disorder and Related Traits.

Andy B Chen, Xuhong Yu, Kriti S Thapa, Hongyu Gao, Jill L Reiter, Xiaoling Xuei, Andy P Tsai, Gary E Landreth, Dongbing Lai, Yue Wang and 4 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Andy B ChenDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Xuhong YuDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Kriti S ThapaDepartment of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
Hongyu GaoDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Jill L ReiterDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Xiaoling XueiDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Andy P TsaiStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana.
Gary E LandrethStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana.
Dongbing LaiDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Yue WangDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Tatiana M ForoudDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Jay A TischfieldDepartment of Genetics, Rutgers University, Piscataway, New Jersey.
Howard J EdenbergDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Yunlong LiuDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.ORCID 0000-0002-2699-626X
Indiana University School of MedicineRutgers, The State University of New Jersey · US

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JAY Arnold TISCHFIELD · 1989 to 2026
$162.7M
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GROSSMAN, HILLEL · 1985 to 2019
$37.9M
QUANTITATIVE ANALYSIS OF MICROVASCULAR CHANGES IN THE AGING BRAINP01AG002219 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HAROUTUNIAN, VAHRAM · 1985 to 2009
$19.2M
White Matter Abnormalities in SchizophreniaP50MH066392 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BUXBAUM, JOSEPH D. · 2002 to 2012
$18.6M
Project 5: In vivo measurement of GABA transmission in healthy controls & subjectP50MH084053 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2008 to 2012
$11.5M
International Cohort Collection for Bipolar DisorderR01MH085542 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SMOLLER, JORDAN W · 2008 to 2012
$10.7M
Cis-Regulatory Epigenome Mappings in SchizophreniaU01MH103392 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, SKLAR, PAMELA · 2014 to 2017
$7.6M
Molecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9M
Genetics Association in Schizophrenia and Other DisordersR37MH057881 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DEVLIN, BERNIE · 2013 to 2022
$5.4M
Risk genetic variants and cis regulation of gene expression in Bipolar DisorderR01MH109677 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2016 to 2020
$4.6M
Src mediates molecular alterations leading to NMDAR hypofunction in schizophreniaR01MH075916 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI HAHN, CHANG-GYU, SIEGEL, STEVEN J · 2006 to 2019
$3.3M
Functional genetic variants in substance use disordersR01DA053722 · NIDA · INDIANA UNIVERSITY INDIANAPOLIS · PI EDENBERG, HOWARD J, LIU, YUNLONG · 2021 to 2025
$3.1M
NCATS NIH HHS TL1 TR002531NIAAA NIH HHS U10 AA008401NIA NIH HHS P01 AG002219NIA NIH HHS P50 AG005138NIDA NIH HHS HHSN271201300031CNIDA NIH HHS R01 DA053722NIMH NIH HHS P50 MH066392NIMH NIH HHS P50 MH084053NIMH NIH HHS R01 MH075916NIMH NIH HHS R01 MH080405NIMH NIH HHS R01 MH085542NIMH NIH HHS R01 MH093725NIMH NIH HHS R01 MH097276NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH109897NIMH NIH HHS R01 MH110921NIMH NIH HHS R37 MH057881NIMH NIH HHS U01 MH103392
6 · The paper itself

Abstract

Although genome-wide association studies (GWAS) have identified loci associated with alcohol consumption and alcohol use disorder (AUD), they do not identify which variants are functional. To approach this, we evaluated the impact of variants in 3' untranslated regions (3'-UTRs) of genes in loci associated with substance use and neurological disorders using a massively parallel reporter assay (MPRA) in neuroblastoma and microglia cells. Functionally impactful variants explained a higher proportion of heritability of alcohol traits than non-functional variants. We identified genes whose 3'UTR activities are associated with AUD and alcohol consumption by combining variant effects from MPRA with GWAS results. We examined their effects by evaluating gene expression after CRISPR inhibition of neuronal cells and stratifying brain tissue samples by MPRA-derived 3'-UTR activity. A pathway analysis of differentially expressed genes identified inflammation response pathways. These analyses suggest that variation in response to inflammation contributes to the propensity to increase alcohol consumption.

Identifiers

PMID38370821
PMCPMC10871301
OpenAlexW4391664837

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.