Evidence map›Paper›PMID 38347632›Full record

ArticleGenome medicine2024

Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study.

Vignesh Arunachalam, Rodney Lea, Wendy Hoy, Simon Lee, Susan Mott, Judith Savige, John D Mathews, Brendan J McMorran, Shivashankar H Nagaraj

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

Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
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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

9 authors at 6 institutions in 1 country.

Vignesh ArunachalamCentre for Genomics and Personalised Health and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Rodney LeaCentre for Genomics and Personalised Health and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Wendy HoyCentre of chronic disease, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Simon LeeCentre for Genomics and Personalised Health and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Susan MottCentre of chronic disease, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Judith SavigeRoyal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.
John D MathewsMelbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Brendan J McMorranNational Centre for Indigenous Genomics, The John Curtin of Medical Research, Australian National University, Canberra, ACT, Australia.
Shivashankar H NagarajCentre for Genomics and Personalised Health and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. shiv.nagaraj@qut.edu.au.ORCID 0000-0003-3463-6835
Queensland University of Technology · AUThe University of Queensland · AUAustralian National University · AUThe Royal Melbourne Hospital · AUThe University of Melbourne · AUTranslational Research Institute · AU

Funding

MRFF Genomics Health Future Mission 76757
6 · The paper itself

Abstract

backgroundChronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations. Despite the identification of numerous genetic loci associated with kidney disease through GWAS, the Indigenous population such as Tiwi remains severely underrepresented and the increased prevalence of CKD in this population may be due to unique disease-causing alleles/genes.

methodsWe used albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) to estimate the prevalence of kidney disease in the Tiwi population (N = 492) in comparison to the UK Biobank (UKBB) (N = 134,724) database. We then performed an exploratory factor analysis to identify correlations among 10 CKD-related phenotypes and identify new multi-phenotype factors. We subsequently conducted a genome-wide association study (GWAS) on all single and multiple phenotype factors using mixed linear regression models, adjusted for age, sex, population stratification, and genetic relatedness between individuals.

resultsBased on ACR, 20.3% of the population was at severely increased risk of CKD progression and showed elevated levels of ACR compared to the UKBB population independent of HbA1c. A GWAS of ACR revealed novel association loci in the genes MEG3 (chr14:100812018:T:A), RAB36 (rs11704318), and TIAM2 (rs9689640). Additionally, multiple phenotypes GWAS of ACR, eGFR, urine albumin, and serum creatinine identified a novel variant that mapped to the gene MEIS2 (chr15:37218869:A:G). Most of the identified variants were found to be either absent or rare in the UKBB population.

conclusionsOur study highlights the Tiwi population's predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to comprehensively validate the functions of the identified variants/genes.

Indexed as

Australian Aboriginal and Torres Strait Islander PeoplesGenome-Wide Association StudyRenal Insufficiency, ChronicAlbuminsAustralasian PeopleAustraliaGenetic MarkersHumansPhenotypeAlbuminsGenetic MarkersAlbumin-to-creatinine ratioChronic Kidney DiseaseGenetic variantIndigenous AustraliansTiwi Island

Identifiers

PMID38347632
PMCPMC10860247
OpenAlexW4391746808

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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.