Evidence map›Paper›PMID 37527041›Full record

ArticleCell reports2023

Genome-wide association studies of human and rat BMI converge on synapse, epigenome, and hormone signaling networks.

Sarah N Wright, Brittany S Leger, Sara Brin Rosenthal, Sophie N Liu, Tongqiu Jia, Apurva S Chitre, Oksana Polesskaya, Katie Holl, Jianjun Gao, Riyan Cheng and 21 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Sarah N WrightDepartment of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA 92093, USA.
Brittany S LegerDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA; Program in Biomedical Sciences, University of California San Diego, La Jolla, CA 93093, USA.
Sara Brin RosenthalCenter for Computational Biology & Bioinformatics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Sophie N LiuDepartment of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Tongqiu JiaDepartment of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Apurva S ChitreDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA.
Oksana PolesskayaDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA.
Katie HollDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Jianjun GaoDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA.
Riyan ChengDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA.
Angel Garcia MartinezDepartment of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Anthony GeorgeClinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
Alexander F GiletaDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Wenyan HanDepartment of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Alesa H NetzleyDepartment of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.
Christopher P KingClinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA; Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
Alexander LamparelliDepartment of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
Connor MartinClinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA; Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
Celine L St PierreDepartment of Genetics, Washington University, St. Louis, MO 63110, USA.
Tengfei WangDepartment of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Hannah BimschlegerDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA.
Jerry RichardsClinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
Keita IshiwariClinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY 14203, USA.
Hao ChenDepartment of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Shelly B FlagelDepartment of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Paul MeyerDepartment of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
Terry E RobinsonDepartment of Psychology, University of Michigan, Ann Arbor, MI 48109, USA.
Leah C Solberg WoodsDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Jason F KreisbergDepartment of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Trey IdekerDepartment of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: tideker@ucsd.edu.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: aap@ucsd.edu.

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Sequencing CoreP50DA037844 · NIDA · UNIVERSITY OF CHICAGO · PI PALMER, ABRAHAM A · 2014 to 2023
$27.4M
The Psychiatric Cell Map Initiative: Connecting Genomics, Subcellular Networks, and Higher Order PhenotypesU01MH115747 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN, KROGAN, NEVAN J · 2018 to 2022
$19.6M
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
UC San Diego Genetics Training ProgramT32GM145427 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRUCE A HAMILTON · 2022 to 2026
$2.6M
NCATS NIH HHS UL1 TR001442NIDA NIH HHS P50 DA037844NIGMS NIH HHS P41 GM103504NIGMS NIH HHS T32 GM008666NIGMS NIH HHS T32 GM145427NIMH NIH HHS U01 MH115747
6 · The paper itself

Abstract

A vexing observation in genome-wide association studies (GWASs) is that parallel analyses in different species may not identify orthologous genes. Here, we demonstrate that cross-species translation of GWASs can be greatly improved by an analysis of co-localization within molecular networks. Using body mass index (BMI) as an example, we show that the genes associated with BMI in humans lack significant agreement with those identified in rats. However, the networks interconnecting these genes show substantial overlap, highlighting common mechanisms including synaptic signaling, epigenetic modification, and hormonal regulation. Genetic perturbations within these networks cause abnormal BMI phenotypes in mice, too, supporting their broad conservation across mammals. Other mechanisms appear species specific, including carbohydrate biosynthesis (humans) and glycerolipid metabolism (rodents). Finally, network co-localization also identifies cross-species convergence for height/body length. This study advances a general paradigm for determining whether and how phenotypes measured in model species recapitulate human biology.

Indexed as

Body Mass IndexGene Regulatory NetworksAnimalsBody SizeGenome-Wide Association StudyHumansMiceRatsSpecies SpecificityBMIbody mass indexCP: Genomicscross-speciesgene networksgenome-wide association studiesGWASheterogeneous stock ratnetworknetwork co-localizationrat

Identifiers

PMID37527041
PMCPMC10546330

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.