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Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease


Tran, NK and Lea, RA and Holland, S and Nguyen, Q and Raghubar, AM and Sutherland, HG and Benton, MC and Haupt, LM and Blackburn, NB and Curran, JE and Blangero, J and Mallett, AJ and Griffiths, LR, Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease, Scientific Reports, 11 Article 19425. ISSN 2045-2322 (2021) [Refereed Article]


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Copyright 2021 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/s41598-021-98935-4


Chronic kidney disease (CKD) is a persistent impairment of kidney function. Genome-wide association studies (GWAS) have revealed multiple genetic loci associated with CKD susceptibility but the complete genetic basis is not yet clear. Since CKD shares risk factors with cardiovascular diseases and diabetes, there may be pleiotropic loci at play but may go undetected when using single phenotype GWAS. Here, we used multi-phenotype GWAS in the Norfolk Island isolate (n = 380) to identify new loci associated with CKD. We performed a principal components analysis on different combinations of 29 quantitative traits to extract principal components (PCs) representative of multiple correlated phenotypes. GWAS of a PC derived from glomerular filtration rate, serum creatinine, and serum urea identified a suggestive peak (pmin = 1.67 x 10-7) that mapped to KCNIP4. Inclusion of other secondary CKD measurements with these three kidney function traits identified the KCNIP4 locus with GWAS significance (pmin = 1.59 x 10-9). Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants. With the use of genetic isolate and the PCA-based multi-phenotype GWAS approach, we have revealed a potential pleotropic effect locus for CKD. Further studies are required to assess functional relevance of this locus.

Item Details

Item Type:Refereed Article
Keywords:chronic kidney disease, genome‑wide association studies, genetics
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Medical genetics (excl. cancer genetics)
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Blackburn, NB (Dr Nicholas Blackburn)
ID Code:152566
Year Published:2021
Deposited By:Research Performance and Analysis
Deposited On:2022-08-22
Last Modified:2022-09-20
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