Evidence map›Paper›PMID 33231259›Full record

ArticleThe Journal of clinical endocrinology and metabolism2021

A Noncoding Variant Near PPP1R3B Promotes Liver Glycogen Storage and MetS, but Protects Against Myocardial Infarction.

Bratati Kahali, Yue Chen, Mary F Feitosa, Lawrence F Bielak, Jeffrey R O'Connell, Solomon K Musani, Yash Hegde, Yanhua Chen, L C Stetson, Xiuqing Guo and 36 more

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

Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 4 pooled it
1.7field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 4 syntheses or guidelines pooled it, 19 citations in OpenAlex.

  1. Pooled it
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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

46 authors at 16 institutions in 4 countries.

Bratati KahaliDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Yue ChenDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Mary F FeitosaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Lawrence F BielakSchool of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Jeffrey R O'ConnellDepartment of Endocrinology, Diabetes, and Nutrition, University of Maryland-Baltimore, Baltimore, MD, USA.
Solomon K MusaniDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Yash HegdeDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Yanhua ChenDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
L C StetsonDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Xiuqing GuoInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics at Harbor-UCLA, Torrance, CA, USA.
Yi-Ping FuFramingham Heart Study, NHLBI, NIH, Framingham, MA, USA.
Albert Vernon SmithSchool of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Kathleen A RyanDepartment of Endocrinology, Diabetes, and Nutrition, University of Maryland-Baltimore, Baltimore, MD, USA.
Gudny EiriksdottirIcelandic Heart Association, Kopavogur, Iceland.
Ariella T CohainDepartment of Genetics and Genomics Sciences, Icahn School of Medicine, New York, NY, USA.
Matthew AllisonDepartment of Family Medicine and Public Health, University of California, San Diego, CA, USA.
Andrew BakshiQueensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Donald W BowdenDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Matthew J BudoffDepartment of Internal Medicine, LA Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA.
J Jeffrey CarrDepartment of Radiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Shannon CarskadonDepartment of Urology, Henry Ford Health System, Detroit, MI, USA.
Yii-Der I ChenInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics at Harbor-UCLA, Torrance, CA, USA.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Breland F CrudupDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Xiaomeng DuDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, National Institute of Aging, Bethesda, MD, USA.
Jian YangQueensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Sharon L R KardiaSchool of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, National Institute of Aging, Bethesda, MD, USA.
Jiankang LiuBrigham and Women's Hospital, Havard University, Boston, MA, USA.
Thomas H MosleyDepartment of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA.
Jill M NorrisDepartment of Preventive Medicine and Biometrics, University of Colorado at Denver Health Sciences Center, Aurora, CO, USA.
James G TerryDepartment of Radiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Nallasivam PalanisamyDepartment of Urology, Henry Ford Health System, Detroit, MI, USA.
Eric E SchadtDepartment of Genetics and Genomics Sciences, Icahn School of Medicine, New York, NY, USA.
Christopher J O'DonnellFramingham Heart Study, NHLBI, NIH, Framingham, MA, USA.
Laura M Yerges-ArmstrongDepartment of Endocrinology, Diabetes, and Nutrition, University of Maryland-Baltimore, Baltimore, MD, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics at Harbor-UCLA, Torrance, CA, USA.
Lynne E WagenknechtDivision of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Samuel K HandelmanDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland.
Michael A ProvinceDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Patricia A PeyserSchool of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Brian HalliganDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Elizabeth K SpeliotesDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
University of Michigan · USThe Lundquist Institute · USJackson Memorial Hospital · USUniversity of Maryland, Baltimore · USWake Forest University · USHenry Ford Health System · USNational Institute on Aging · USThe University of Queensland · AUVanderbilt University · USBrigham and Women's Hospital · USDenver Health Medical Center · USIcelandic Heart Association · ISNational Heart Lung and Blood Institute · USUniversity of California San Diego · USUniversity of Iceland · ISUniversity of Mississippi Medical Center · US

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
Multi-Ethnic Study of Atherosclerosis (MESA) StudyR01HL071205 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2003 to 2007
$10.4M
Creating a National Resource for Genetic Research in Behavioral & Health SciencesRC2AG036495 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WEIR, DAVID R. · 2009 to 2010
$7.4M
The Family Blood Pressure Program (GENOA Network)U01HL054481 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A · 2000 to 2007
$6.7M
Expanding a National Resource for Genetic Research in Behavioral & Health ScienceRC4AG039029 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WEIR, DAVID R. · 2010 to 2010
$6.0M
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR033176NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL060894NHLBI NIH HHS R01 HL060919NHLBI NIH HHS R01 HL060944NHLBI NIH HHS R01 HL061019NHLBI NIH HHS R01 HL061210NHLBI NIH HHS R01 HL071051NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01 HL071250NHLBI NIH HHS R01 HL071251NHLBI NIH HHS R01 HL071258NHLBI NIH HHS R01 HL071259NHLBI NIH HHS R01 HL085571NHLBI NIH HHS R01 HL087660NHLBI NIH HHS R01 HL117078NHLBI NIH HHS U01 HL054457NHLBI NIH HHS U01 HL054464NHLBI NIH HHS U01 HL054481NHLBI NIH HHS U10 HL054457NHLBI NIH HHS U10 HL054464NHLBI NIH HHS U10 HL054481NIA NIH HHS RC2 AG036495NIA NIH HHS RC4 AG039029NIA NIH HHS U01 AG009740NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK089256NIDDK NIH HHS R01 DK106621NIDDK NIH HHS R01 DK107904WHI NIH HHS N01 WH022110
6 · The paper itself

Abstract

contextGlycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation.

objectiveInvestigate the association and function of a noncoding region associated with liver attenuation but not histologic nonalcoholic fatty liver disease.

designGenetics of Obesity-associated Liver Disease Consortium.

settingPopulation-based. MAIN OUTCOME: Computed tomography measured liver attenuation.

resultsCarriers of rs4841132-A (frequency 2%-19%) do not show increased hepatic steatosis; they have increased liver attenuation indicative of increased glycogen deposition. rs4841132 falls in a noncoding RNA LOC157273 ~190 kb upstream of PPP1R3B. We demonstrate that rs4841132-A increases PPP1R3B through a cis genetic effect. Using CRISPR/Cas9 we engineered a 105-bp deletion including rs4841132-A in human hepatocarcinoma cells that increases PPP1R3B, decreases LOC157273, and increases glycogen perfectly mirroring the human disease. Overexpression of PPP1R3B or knockdown of LOC157273 increased glycogen but did not result in decreased LOC157273 or increased PPP1R3B, respectively, suggesting that the effects may not all occur via affecting RNA levels. Based on electronic health record (EHR) data, rs4841132-A associates with all components of the metabolic syndrome (MetS). However, rs4841132-A associated with decreased low-density lipoprotein (LDL) cholesterol and risk for myocardial infarction (MI). A metabolic signature for rs4841132-A includes increased glycine, lactate, triglycerides, and decreased acetoacetate and beta-hydroxybutyrate.

conclusionsThese results show that rs4841132-A promotes a hepatic glycogen storage disease by increasing PPP1R3B and decreasing LOC157273. rs4841132-A promotes glycogen accumulation and development of MetS but lowers LDL cholesterol and risk for MI. These results suggest that elevated hepatic glycogen is one cause of MetS that does not invariably promote MI.

Indexed as

Polymorphism, Single NucleotideAdultAgedBiomarkersFemaleFollow-Up StudiesGlycogen Storage DiseaseHumansLiver GlycogenMaleMetabolic SyndromeMiddle AgedMyocardial InfarctionPrognosisProspective StudiesProtein Phosphatase 1BiomarkersLiver GlycogenPPP1R3B protein, humanProtein Phosphatase 1geneticsglycogenGWASmetabolic syndromeNALFDtriglyceride

Identifiers

PMID33231259
PMCPMC7823249
OpenAlexW3109876921

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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.