Evidence map›Paper›PMID 29097680›Full record

ArticleNature communications2017

Epigenome-wide association studies identify DNA methylation associated with kidney function.

Audrey Y Chu, Adrienne Tin, Pascal Schlosser, Yi-An Ko, Chengxiang Qiu, Chen Yao, Roby Joehanes, Morgan E Grams, Liming Liang, Caroline A Gluck and 11 more

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

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 4 pooled it
7.9field-weighted citation impact, top 2% 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

132 citing papers in PubMed, 4 syntheses or guidelines pooled it, 203 citations in OpenAlex.

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72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 9 institutions in 2 countries.

Audrey Y ChuThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
Adrienne TinDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Pascal SchlosserInstitute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, 79106, Freiburg, Germany.ORCID http://orcid.org/0000-0002-8460-0462
Yi-An KoRenal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Chengxiang QiuRenal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Chen YaoThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
Roby JoehanesThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0001-5549-9054
Morgan E GramsDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Liming LiangDepartment of Biostatistics, Harvard University School of Public Health, Boston, MA, 02115, USA.
Caroline A GluckRenal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0003-1880-2506
Chunyu LiuThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
Josef CoreshDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0002-4598-0669
Shih-Jen HwangThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
Daniel LevyThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
Eric BoerwinkleHuman Genetics Center, University of Texas Health Science Center, Houston, TX, 77030, USA.
James S PankowDivision of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
Qiong YangNHLBI's Framingham Heart Study, Framingham, MA, 01702, USA.ORCID http://orcid.org/0000-0002-3658-1375
Myriam FornageHuman Genetics Center, University of Texas Health Science Center, Houston, TX, 77030, USA.
Caroline S FoxThe Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
Katalin SusztakRenal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Anna KöttgenDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. anna.koettgen@uniklinik-freiburg.de.
Framingham Heart Study · USJohns Hopkins University · USUniversity of Pennsylvania · USThe University of Texas Health Science Center at Houston · USBeth Israel Deaconess Medical Center · USBoston University · USHarvard University · USUniversity of Freiburg · DEUniversity of Minnesota · US

Funding

Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
Transgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI CORKEY, BARBARA E. · 1992 to 2021
$25.0M
Role of the Notch Pathway in Kidney InjuryR01DK076077 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2007 to 2026
$8.0M
Epigenetics of Chronic Kidney DiseaseR01DK087635 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2009 to 2026
$7.0M
Epigenetic drivers and biomarkers of diabetic kidney diseaseDP3DK108220 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2015 to 2015
$2.4M
Risk of Chronic Kidney Disease Associated with GSTM1 DeletionsR21DK112087 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TIN, ADRIENNE · 2016 to 2017
$367k
Characterizing the Epigenome in Chronic Kidney DiseaseF32DK112635 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI GLUCK, CAROLINE ANNE · 2016 to 2016
$62k
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS N01 HC025195NHLBI NIH HHS RC2 HL102419NIDDK NIH HHS DP3 DK108220NIDDK NIH HHS F32 DK112635NIDDK NIH HHS P30 DK046200NIDDK NIH HHS R01 DK076077NIDDK NIH HHS R01 DK087635NIDDK NIH HHS R21 DK112087
6 · The paper itself

Abstract

Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.

Indexed as

AgedBinding SitesCCAAT-Enhancer-Binding Protein-betaCpG IslandsDisease ProgressionDNA MethylationE1A-Associated p300 ProteinEpigenesis, GeneticFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGlomerular Filtration RateHumansKidneyMaleMiddle AgedCCAAT-Enhancer-Binding Protein-betaCEBPB protein, humanE1A-Associated p300 ProteinEBF1 protein, humanEP300 protein, humanPHB2 protein, humanProhibitinsProtein Tyrosine Phosphatase, Non-Receptor Type 6PTPN6 protein, humanTrans-ActivatorsTranscription Factors

Identifiers

PMID29097680
PMCPMC5668367
OpenAlexW2766367869

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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.