Imputation-powered whole-exome analysis identifies genes associated with kidney function and disease in the UK Biobank

Genome-wide association studies have discovered hundreds of associations between common genotypes and kidney function but cannot comprehensively investigate rare coding variants. Here, we apply a genotype imputation approach to whole exome sequencing data from the UK Biobank to increase sample size...

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Vydáno v:Nature communications Ročník 14; číslo 1; s. 1287 - 16
Hlavní autoři: Wuttke, Matthias, König, Eva, Katsara, Maria-Alexandra, Kirsten, Holger, Farahani, Saeed Khomeijani, Teumer, Alexander, Li, Yong, Lang, Martin, Göcmen, Burulca, Pattaro, Cristian, Günzel, Dorothee, Köttgen, Anna, Fuchsberger, Christian
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 09.03.2023
Nature Publishing Group
Nature Portfolio
Témata:
49/23
631/208/205/2138
692/4022/1585/104
Alleles
Biobanks
Biological Specimen Banks
Exome - genetics
Genes
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotypes
Humanities and Social Sciences
Humans
Kidney
Kidney diseases
Kidneys
multidisciplinary
Mutation
Polymorphism, Single Nucleotide
Science
Science (multidisciplinary)
United Kingdom
United Kingdom
United Kingdom > UK
ISSN:2041-1723, 2041-1723
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Shrnutí:Genome-wide association studies have discovered hundreds of associations between common genotypes and kidney function but cannot comprehensively investigate rare coding variants. Here, we apply a genotype imputation approach to whole exome sequencing data from the UK Biobank to increase sample size from 166,891 to 408,511. We detect 158 rare variants and 105 genes significantly associated with one or more of five kidney function traits, including genes not previously linked to kidney disease in humans. The imputation-powered findings derive support from clinical record-based kidney disease information, such as for a previously unreported splice allele in PKD2 , and from functional studies of a previously unreported frameshift allele in CLDN10 . This cost-efficient approach boosts statistical power to detect and characterize both known and novel disease susceptibility variants and genes, can be generalized to larger future studies, and generates a comprehensive resource ( https://ckdgen-ukbb.gm.eurac.edu/ ) to direct experimental and clinical studies of kidney disease. An exome wide association study of UK Biobank data revealed 158 variants and 105 genes significantly associated with kidney function traits and disease. The findings are supported by functional evidence for a previously unreported mutation in CLDN10.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-36864-8