Evidence map›Paper›PMID 37746849›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2023

Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies.

Jeremiah Martino, Qingxue Liu, Katarina Vukojevic, Juntao Ke, Tze Y Lim, Atlas Khan, Yask Gupta, Alejandra Perez, Zonghai Yan, Hila Milo Rasouly and 21 more

Open access · bronzeAbstract read
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

31 authors at 7 institutions in 7 countries.

Jeremiah MartinoDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Qingxue LiuDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Katarina VukojevicDepartment of Medicine, Columbia University Irving Medical Center, New York, NY; Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Split, Croatia.
Juntao KeDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Tze Y LimDepartment of Medicine, Columbia University Irving Medical Center, New York, NY; Unit of Genomic Variability and Complex Diseases, Department of Medical Sciences, University of Turin, Turin, Italy.
Atlas KhanDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Yask GuptaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY; Institute for Inflammation Medicine, University of Lubeck, Germany.
Alejandra PerezDepartment of Medicine, Columbia University Irving Medical Center, New York, NY; Department of Urology, Mount Sinai Medical Center, Miami, FL.
Zonghai YanDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Hila Milo RasoulyDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Natalie VenaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Natalie LippaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Jessica L GiordanoObstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY.
Marijan SaragaDepartment of Pediatrics, University Hospital of Split, Split, Croatia; School of Medicine, University of Split, Split, Croatia.
Mirna Saraga-BabicDepartment of Anatomy, Histology and Embryology, University of Split School of Medicine, Split, Croatia.
Rik WestlandDepartment of Pediatric Nephrology, Emma Children's Hospital, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Monica BodriaDivision of Nephrology and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy; Laboratory on Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Giorgio PiaggioDivision of Nephrology and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy; Laboratory on Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Pavan K BendapudiDivision of Hematology and Blood Transfusion Service, Massachusetts General Hospital, Boston, MA; Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA.
Alejandro D IglesiasDepartment of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.
Ronald J WapnerObstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY.
Velibor TasicMedical Faculty of Skopje, University Children's Hospital, Skopje, Macedonia.
Fan WangDepartment of Biostatistics, Columbia University, New York, NY.
Iuliana Ionita-LazaDepartment of Biostatistics, Columbia University, New York, NY.
Gian Marco GhiggeriDivision of Nephrology and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy; Laboratory on Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Krzysztof KirylukDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Rosemary V SampognaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Cathy L MendelsohnDepartment of Urology, Columbia University Irving Medical Center, New York, NY; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY.
Vivette D D'AgatiThe Renal Pathology Laboratory of the Department of Pathology and Cell Biology, Columbia University, New York, NY.
Ali G GharaviDepartment of Medicine, Columbia University Irving Medical Center, New York, NY.
Simone Sanna-CherchiDepartment of Medicine, Columbia University Irving Medical Center, New York, NY. Electronic address: ss2517@cumc.columbia.edu.
Columbia University Irving Medical Center · USColumbia University · USIstituto Giannina Gaslini · ITUniversity of Split · HRBeth Israel Deaconess Medical Center · USChildren's Clinical University Hospital · LVEmma Kinderziekenhuis · NL

Funding

Transcriptional Regulation of Urothelial Differentiation During Homeostasis and Repair in Response to Urinary Tract InfectionU54DK104309 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JONATHAN M. BARASCH, ALI G GHARAVI · 2014 to 2026
$17.7M
Genetics of Renal HypodyslasiaR01DK080099 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GHARAVI, ALI G · 2008 to 2023
$6.3M
Genomics of mammalian posterior urethral valvesR01DK115574 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SANNA-CHERCHI, SIMONE · 2017 to 2021
$2.9M
Genetics of Congenital Obstructive UropathyR01DK103184 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SANNA-CHERCHI, SIMONE · 2014 to 2018
$2.3M
Training Medical Students in NIDDK ResearchT35DK093430 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI QAIS AL-AWQATI, Utpal Pajvani · 2012 to 2026
$1.3M
Predictive utility of polygenic risk scores for chronic kidney disease.K25DK128563 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KHAN, ATLAS · 2021 to 2025
$846k
Novel genomic and transcriptomic tools to study human congenital anomalies of the kidney and urinary tractP20DK116191 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SANNA-CHERCHI, SIMONE · 2018 to 2019
$644k
Genetic and Molecular Etiology of Developmental Kidney and Urinary Tract Abnormalities in the DiGeorge, or 22q11.2, Syndrome.F32DK121454 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MARTINO, JEREMIAH · 2019 to 2021
$216k
NIDDK NIH HHS F32 DK121454NIDDK NIH HHS K25 DK128563NIDDK NIH HHS P20 DK116191NIDDK NIH HHS R01 DK080099NIDDK NIH HHS R01 DK103184NIDDK NIH HHS R01 DK115574NIDDK NIH HHS T35 DK093430NIDDK NIH HHS U54 DK104309
6 · The paper itself

Abstract

purposePrevious work identified rare variants in DSTYK associated with human congenital anomalies of the kidney and urinary tract (CAKUT). Here, we present a series of mouse and human studies to clarify the association, penetrance, and expressivity of DSTYK variants.

methodsWe phenotypically characterized Dstyk knockout mice of 3 separate inbred backgrounds and re-analyzed the original family segregating the DSTYK c.654+1G>A splice-site variant (referred to as "SSV" below). DSTYK loss of function (LOF) and SSVs were annotated in individuals with CAKUT, epilepsy, or amyotrophic lateral sclerosis vs controls. A phenome-wide association study analysis was also performed using United Kingdom Biobank (UKBB) data.

resultsResults demonstrate ∼20% to 25% penetrance of obstructive uropathy, at least, in C57BL/6J and FVB/NJ Dstyk

conclusionThese data support causality for DSTYK LOF variants and highlights the need for large-scale sequencing studies (here >200,000 cases) to accurately assess causality for genes and variants to lowly penetrant traits with common population prevalence.

Indexed as

EpilepsyUrinary TractUrogenital AbnormalitiesAnimalsHumansKidneyMiceMice, Inbred C3HMice, Inbred C57BLPenetranceReceptor-Interacting Protein Serine-Threonine KinasesRisk FactorsVesico-Ureteral RefluxDSTYK protein, humanReceptor-Interacting Protein Serine-Threonine KinasesCongenital anomalies of the kidney and urinary tractCongenital obstructive uropathyDevelopmental kidney diseaseDSTYKMouse models of kidney disease

Identifiers

PMID37746849
PMCPMC13372018
OpenAlexW4386913492

What Socratic 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 Socratic graph.