Evidence map›Paper›PMID 25573024›Full record

ArticleCirculation. Cardiovascular genetics2015

Systems biology with high-throughput sequencing reveals genetic mechanisms underlying the metabolic syndrome in the Lyon hypertensive rat.

Jinkai Wang, Man Chun John Ma, Amanda K Mennie, Janette M Pettus, Yang Xu, Lan Lin, Matthew G Traxler, Jessica Jakoubek, Santosh S Atanur, Timothy J Aitman and 2 more

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

Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  7. Review
  8. Rat Models of Metabolic Syndrome.Methods in molecular biology (Clifton, N.J.) · 2019
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  16. PhenoGeneRanker: Gene and Phenotype Prioritization Using Multiplex Heterogeneous Networks.IEEE/ACM transactions on computational biology and bioinformatics
    Article
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

12 authors at 1 institution in 1 country.

Jinkai WangFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Man Chun John MaFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Amanda K MennieFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Janette M PettusFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Yang XuFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Lan LinFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Matthew G TraxlerFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Jessica JakoubekFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Santosh S AtanurFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Timothy J AitmanFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.).
Yi XingFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.). anne-kwitek@uiowa.edu yxing@ucla.edu.
Anne E KwitekFrom the Department of Internal Medicine (J.W., A.K.M., J.M.P., Y. Xu, L.L., Y. Xing, A.E.K.), Department of Pharmacology (M.C.J.M., A.K.M., J.M.P., Y. Xu, M.G.T., J.J., A.E.K.), and Iowa Institute of Human Genetics (A.E.K.), University of Iowa, Iowa City; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (J.W., L.L., Y. Xing); and Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom (S.S.A., T.J.A.). anne-kwitek@uiowa.edu yxing@ucla.edu.
University of California, Los Angeles · US

Funding

SHORT-TERM TRAINING: STUDENTS IN HEALTH PROF. SCHOOLST35HL007485 · NHLBI · UNIVERSITY OF IOWA · PI ROGHAIR, ROBERT D · 1985 to 2019
$4.3M
Dissecting the genetics of the Metabolic Syndrome on Chromosome 17 of the LH ratR01HL089895 · NHLBI · UNIVERSITY OF IOWA · PI KWITEK, ANNE E. · 2008 to 2012
$1.7M
Identification of a metabolic syndrome transcriptome signature in the LH ratR21DK089417 · NIDDK · UNIVERSITY OF IOWA · PI KWITEK, ANNE E., XING, YI · 2010 to 2011
$411k
Medical Research Council MC_U120061454NHLBI NIH HHS R01 HL089895NHLBI NIH HHS R01HL089895NHLBI NIH HHS T35 HL007485NIDDK NIH HHS R21 DK089417NIDDK NIH HHS R21DK089417
6 · The paper itself

Abstract

backgroundThe metabolic syndrome (MetS) is a collection of co-occurring complex disorders including obesity, hypertension, dyslipidemia, and insulin resistance. The Lyon hypertensive and Lyon normotensive rats are models of MetS sensitivity and resistance, respectively. To identify genetic determinants and mechanisms underlying MetS, an F2 intercross between Lyon hypertensive and Lyon normotensive was comprehensively studied. METHODS AND

resultsMultidimensional data were obtained including genotypes of 1536 single-nucleotide polymorphisms, 23 physiological traits, and >150 billion nucleotides of RNA-seq reads from the livers of F2 intercross offspring and parental rats. Phenotypic and expression quantitative trait loci (eQTL) were mapped. Application of systems biology methods identified 17 candidate MetS genes. Several putative causal cis-eQTL were identified corresponding with phenotypic QTL loci. We found an eQTL hotspot on rat chromosome 17 that is causally associated with multiple MetS-related traits and found RGD1562963, a gene regulated in cis by this eQTL hotspot, as the most likely eQTL driver gene directly affected by genetic variation between Lyon hypertensive and Lyon normotensive rats.

conclusionsOur study sheds light on the intricate pathogenesis of MetS and demonstrates that systems biology with high-throughput sequencing is a powerful method to study the pathogenesis of complex genetic diseases.

Indexed as

Polymorphism, Single NucleotideQuantitative Trait LociAnimalsChromosomes, MammalianHypertensionMetabolic SyndromeRatsSystems Biologygeneticssystems biologytranscriptome

Identifiers

PMID25573024
PMCPMC4406788
OpenAlexW2124748700

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