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

Abstract 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 diseas...

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Autores principales:	Ngan K. Tran, Rodney A. Lea, Samuel Holland, Quan Nguyen, Arti M. Raghubar, Heidi G. Sutherland, Miles C. Benton, Larisa M. Haupt, Nicholas B. Blackburn, Joanne E. Curran, John Blangero, Andrew J. Mallett, Lyn R. Griffiths
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08009bcdb0694bb7ba1a1392cc5bb0b2
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spelling	oai:doaj.org-article:08009bcdb0694bb7ba1a1392cc5bb0b22021-12-02T17:17:39ZMulti-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease10.1038/s41598-021-98935-42045-2322https://doaj.org/article/08009bcdb0694bb7ba1a1392cc5bb0b22021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98935-4https://doaj.org/toc/2045-2322Abstract 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 × 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 × 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.Ngan K. TranRodney A. LeaSamuel HollandQuan NguyenArti M. RaghubarHeidi G. SutherlandMiles C. BentonLarisa M. HauptNicholas B. BlackburnJoanne E. CurranJohn BlangeroAndrew J. MallettLyn R. GriffithsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ngan K. Tran Rodney A. Lea Samuel Holland Quan Nguyen Arti M. Raghubar Heidi G. Sutherland Miles C. Benton Larisa M. Haupt Nicholas B. Blackburn Joanne E. Curran John Blangero Andrew J. Mallett Lyn R. Griffiths Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
description	Abstract 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 × 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 × 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.
format	article
author	Ngan K. Tran Rodney A. Lea Samuel Holland Quan Nguyen Arti M. Raghubar Heidi G. Sutherland Miles C. Benton Larisa M. Haupt Nicholas B. Blackburn Joanne E. Curran John Blangero Andrew J. Mallett Lyn R. Griffiths
author_facet	Ngan K. Tran Rodney A. Lea Samuel Holland Quan Nguyen Arti M. Raghubar Heidi G. Sutherland Miles C. Benton Larisa M. Haupt Nicholas B. Blackburn Joanne E. Curran John Blangero Andrew J. Mallett Lyn R. Griffiths
author_sort	Ngan K. Tran
title	Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
title_short	Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
title_full	Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
title_fullStr	Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
title_full_unstemmed	Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
title_sort	multi-phenotype genome-wide association studies of the norfolk island isolate implicate pleiotropic loci involved in chronic kidney disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/08009bcdb0694bb7ba1a1392cc5bb0b2
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Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease

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