Evidence map›Paper›PMID 38671065›Full record

ArticleScientific reports2024

A clustering approach to improve our understanding of the genetic and phenotypic complexity of chronic kidney disease.

A Eoli, S Ibing, C Schurmann, G N Nadkarni, H O Heyne, E Böttinger

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Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

A Eoli *Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482. andrea.eoli@hpi.de.
S Ibing *Digital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482.
C SchurmannDigital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482.
G N NadkarniWindreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
H O HeyneDigital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482.
E BöttingerDigital Engineering Faculty, University of Potsdam, Potsdam, Germany, Prof.-Dr.-Helmert-Str. 2-3, 14482.

Funding

Conduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4M
Diverse ancestry biobank to map biomedical traits and elucidate health disparitieU01HG007417 · NHGRI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI LOOS, RUTH JF · 2013 to 2017
$3.5M
COVID and Translational Science supercomputer (CATS)S10OD030463 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2021 to 2021
$2.0M
Big Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0M
NCATS NIH HHS UL1 TR004419NHGRI NIH HHS U01 HG007417NIH HHS S10 OD026880NIH HHS S10 OD030463
6 · The paper itself

Abstract

Chronic kidney disease (CKD) is a complex disorder that causes a gradual loss of kidney function, affecting approximately 9.1% of the world's population. Here, we use a soft-clustering algorithm to deconstruct its genetic heterogeneity. First, we selected 322 CKD-associated independent genetic variants from published genome-wide association studies (GWAS) and added association results for 229 traits from the GWAS catalog. We then applied nonnegative matrix factorization (NMF) to discover overlapping clusters of related traits and variants. We computed cluster-specific polygenic scores and validated each cluster with a phenome-wide association study (PheWAS) on the BioMe biobank (n = 31,701). NMF identified nine clusters that reflect different aspects of CKD, with the top-weighted traits signifying areas such as kidney function, type 2 diabetes (T2D), and body weight. For most clusters, the top-weighted traits were confirmed in the PheWAS analysis. Results were found to be more significant in the cross-ancestry analysis, although significant ancestry-specific associations were also identified. While all alleles were associated with a decreased kidney function, associations with CKD-related diseases (e.g., T2D) were found only for a smaller subset of variants and differed across genetic ancestry groups. Our findings leverage genetics to gain insights into the underlying biology of CKD and investigate population-specific associations.

Indexed as

Genome-Wide Association StudyPhenotypeRenal Insufficiency, ChronicAlgorithmsCluster AnalysisDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseHumansMaleMultifactorial InheritancePolymorphism, Single Nucleotide

Identifiers

PMID38671065
PMCPMC11053134

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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.