Quantifying variant contributions in cystic kidney disease using national-scale whole-genome sequencing
BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry...
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Published in | The Journal of clinical investigation Vol. 134; no. 19; pp. 1 - 14 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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American Society for Clinical Investigation
01.10.2024
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Abstract | BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies.RESULTSIn 82.3% of cases, a qualifying potentially disease-causing rare variant in an established gene was found. There was an enrichment of rare coding, splicing, and structural variants in known CyKD genes, with statistically significant gene-based signals in COL4A3 and (monoallelic) PKHD1. Quantification of disease risk for each gene (with replication in the separate UK Biobank study) revealed substantially lower risk associated with genes more recently associated with autosomal dominant polycystic kidney disease, with odds ratios for some below what might usually be regarded as necessary for classical Mendelian inheritance. Meta-analysis of common variants did not reveal significant associations, but suggested this category of variation contributes 3%-9% to the heritability of CyKD across European ancestries.CONCLUSIONBy providing unbiased quantification of risk effects per gene, this research suggests that not all rare variant genetic contributors to CyKD are equally likely to manifest as a Mendelian trait in families. This information may inform genetic testing and counseling in the clinic. |
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AbstractList | BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies.RESULTSIn 82.3% of cases, a qualifying potentially disease-causing rare variant in an established gene was found. There was an enrichment of rare coding, splicing, and structural variants in known CyKD genes, with statistically significant gene-based signals in COL4A3 and (monoallelic) PKHD1. Quantification of disease risk for each gene (with replication in the separate UK Biobank study) revealed substantially lower risk associated with genes more recently associated with autosomal dominant polycystic kidney disease, with odds ratios for some below what might usually be regarded as necessary for classical Mendelian inheritance. Meta-analysis of common variants did not reveal significant associations, but suggested this category of variation contributes 3%-9% to the heritability of CyKD across European ancestries.CONCLUSIONBy providing unbiased quantification of risk effects per gene, this research suggests that not all rare variant genetic contributors to CyKD are equally likely to manifest as a Mendelian trait in families. This information may inform genetic testing and counseling in the clinic. BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies.RESULTSIn 82.3% of cases, a qualifying potentially disease-causing rare variant in an established gene was found. There was an enrichment of rare coding, splicing, and structural variants in known CyKD genes, with statistically significant gene-based signals in COL4A3 and (monoallelic) PKHD1. Quantification of disease risk for each gene (with replication in the separate UK Biobank study) revealed substantially lower risk associated with genes more recently associated with autosomal dominant polycystic kidney disease, with odds ratios for some below what might usually be regarded as necessary for classical Mendelian inheritance. Meta-analysis of common variants did not reveal significant associations, but suggested this category of variation contributes 3%-9% to the heritability of CyKD across European ancestries.CONCLUSIONBy providing unbiased quantification of risk effects per gene, this research suggests that not all rare variant genetic contributors to CyKD are equally likely to manifest as a Mendelian trait in families. This information may inform genetic testing and counseling in the clinic.BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies.RESULTSIn 82.3% of cases, a qualifying potentially disease-causing rare variant in an established gene was found. There was an enrichment of rare coding, splicing, and structural variants in known CyKD genes, with statistically significant gene-based signals in COL4A3 and (monoallelic) PKHD1. Quantification of disease risk for each gene (with replication in the separate UK Biobank study) revealed substantially lower risk associated with genes more recently associated with autosomal dominant polycystic kidney disease, with odds ratios for some below what might usually be regarded as necessary for classical Mendelian inheritance. Meta-analysis of common variants did not reveal significant associations, but suggested this category of variation contributes 3%-9% to the heritability of CyKD across European ancestries.CONCLUSIONBy providing unbiased quantification of risk effects per gene, this research suggests that not all rare variant genetic contributors to CyKD are equally likely to manifest as a Mendelian trait in families. This information may inform genetic testing and counseling in the clinic. This research challenges traditional definitions of monogenic diseases by demonstrating varied genetic risk factors for cystic kidney disease, suggesting a complex interplay beyond simple Mendelian inheritance. BACKGROUND. Cystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases. METHODS. Using whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies. RESULTS. In 82.3% of cases, a qualifying potentially disease-causing rare variant in an established gene was found. There was an enrichment of rare coding, splicing, and structural variants in known CyKD genes, with statistically significant gene-based signals in COL4A3 and (monoallelic) PKHD1. Quantification of disease risk for each gene (with replication in the separate UK Biobank study) revealed substantially lower risk associated with genes more recently associated with autosomal dominant polycystic kidney disease, with odds ratios for some below what might usually be regarded as necessary for classical Mendelian inheritance. Meta-analysis of common variants did not reveal significant associations, but suggested this category of variation contributes 3%-9% to the heritability of CyKD across European ancestries. CONCLUSION. By providing unbiased quantification of risk effects per gene, this research suggests that not all rare variant genetic contributors to CyKD are equally likely to manifest as a Mendelian trait in families. This information may inform genetic testing and counseling in the clinic. |
Audience | Academic |
Author | Voinescu, Catalin D Kousathanas, Athanasios Stanescu, Horia C Sandford, Richard N Stuckey, Alexander Chan, Melanie My Sadeghi-Alavijeh, Omid Doctor, Gabriel T Bockenhauer, Detlef Ho, Alexander T Levine, Adam P Gale, Daniel P |
AuthorAffiliation | 1 Centre for Kidney and Bladder Health, University College London, London, United Kingdom 5 Academic Department of Medical Genetics, Cambridge University, Cambridge, United Kingdom 4 University Hospital and Katholic University Leuven, Leuven, Belgium 2 Genomics England, Queen Mary University of London, London, United Kingdom 3 Research Department of Pathology, University College London, London, United Kingdom |
AuthorAffiliation_xml | – name: 2 Genomics England, Queen Mary University of London, London, United Kingdom – name: 1 Centre for Kidney and Bladder Health, University College London, London, United Kingdom – name: 4 University Hospital and Katholic University Leuven, Leuven, Belgium – name: 3 Research Department of Pathology, University College London, London, United Kingdom – name: 5 Academic Department of Medical Genetics, Cambridge University, Cambridge, United Kingdom |
Author_xml | – sequence: 1 givenname: Omid surname: Sadeghi-Alavijeh fullname: Sadeghi-Alavijeh, Omid organization: Centre for Kidney and Bladder Health, University College London, London, United Kingdom – sequence: 2 givenname: Melanie My surname: Chan fullname: Chan, Melanie My organization: Centre for Kidney and Bladder Health, University College London, London, United Kingdom – sequence: 3 givenname: Gabriel T surname: Doctor fullname: Doctor, Gabriel T organization: Centre for Kidney and Bladder Health, University College London, London, United Kingdom – sequence: 4 givenname: Catalin D surname: Voinescu fullname: Voinescu, Catalin D organization: Centre for Kidney and Bladder Health, University College London, London, United Kingdom – sequence: 5 givenname: Alexander surname: Stuckey fullname: Stuckey, Alexander organization: Genomics England, Queen Mary University of London, London, United Kingdom – sequence: 6 givenname: Athanasios surname: Kousathanas fullname: Kousathanas, Athanasios organization: Genomics England, Queen Mary University of London, London, United Kingdom – sequence: 7 givenname: Alexander T surname: Ho fullname: Ho, Alexander T organization: Genomics England, Queen Mary University of London, London, United Kingdom – sequence: 8 givenname: Horia C surname: Stanescu fullname: Stanescu, Horia C organization: Centre for Kidney and Bladder Health, University College London, London, United Kingdom – sequence: 9 givenname: Detlef surname: Bockenhauer fullname: Bockenhauer, Detlef organization: University Hospital and Katholic University Leuven, Leuven, Belgium – sequence: 10 givenname: Richard N surname: Sandford fullname: Sandford, Richard N organization: Academic Department of Medical Genetics, Cambridge University, Cambridge, United Kingdom – sequence: 11 givenname: Adam P surname: Levine fullname: Levine, Adam P organization: Research Department of Pathology, University College London, London, United Kingdom – sequence: 12 givenname: Daniel P surname: Gale fullname: Gale, Daniel P organization: Centre for Kidney and Bladder Health, University College London, London, United Kingdom |
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Cites_doi | 10.1681/ASN.2012070650 10.1016/j.ajhg.2022.06.013 10.1073/pnas.2114734119 10.1093/bioinformatics/btw163 10.1101/2022.03.03.22271360 10.1371/journal.pgen.1004269 10.1016/j.ajhg.2017.05.014 10.1038/ki.2015.207 10.1056/NEJMra1312543 10.1172/JCI90129 10.1681/ASN.2013101138 10.1038/s41588-019-0528-2 10.1038/nature19057 10.21105/joss.00731 10.1007/978-981-10-2041-4_2 10.1093/bioinformatics/btq340 10.1093/bioinformatics/btv710 10.1073/pnas.1602743113 10.1038/s41525-023-00362-z 10.1038/nrneph.2009.43 10.1002/humu.22103 10.1016/j.kint.2023.06.019 10.1038/s41588-022-01178-w 10.1038/s41588-020-0621-6 10.1093/ndt/gfv456 10.1093/bioinformatics/btx770 10.1681/ASN.2011101032 10.1038/s41586-020-2287-8 10.2215/CJN.00980208 10.1056/NEJMoa2035790 10.1681/ASN.2015010016 10.1016/j.ajhg.2011.02.002 10.1016/j.ajhg.2016.05.004 10.1681/ASN.2019030298 10.1038/s41431-020-00796-4 10.1093/nar/gkj144 10.1073/pnas.0506580102 10.1093/nar/gkaa1043 10.1016/j.ajhg.2021.02.016 10.1038/ncomms14061 10.1038/s41586-020-2434-2 10.1038/s41586-021-03855-y 10.1016/j.ajhg.2018.03.013 10.1038/ejhg.2016.48 10.1093/bioinformatics/btq033 10.1093/gigascience/giab008 10.1681/ASN.2018050493 10.1016/j.ajhg.2016.08.016 10.1016/j.ajhg.2021.11.016 10.1038/s41467-022-32885-x 10.1101/2023.12.20.23300294 10.1038/s41588-020-0600-y 10.1056/NEJMoa1806891 10.1080/15476286.2015.1014291 10.1002/humu.23223 10.1159/000508558 10.1016/j.ekir.2019.09.004 |
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References | B20 B21 B22 B23 B24 B25 B26 B27 B28 B29 Hinrichs (B45) 2006; 34 B30 B31 B32 B33 B34 B35 B36 B37 B38 B39 B2 B3 B4 B5 B6 B7 B8 B9 B40 B41 B42 B43 B44 B46 B47 B48 B49 B50 B51 B52 B53 B10 B54 B11 B55 B12 B56 B13 B57 B14 B58 B15 B59 B16 B17 Evans (B1) 2018; 139 B18 B19 B60 B61 B62 B63 |
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Snippet | BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an... BACKGROUND. Cystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies,... This research challenges traditional definitions of monogenic diseases by demonstrating varied genetic risk factors for cystic kidney disease, suggesting a... |
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SubjectTerms | Autoantigens Case-Control Studies Clinical Medicine Collagen Type IV - genetics Cysts DNA sequencing Female Gene Frequency Genes Genetic aspects Genetic Predisposition to Disease Genetic testing Genetic Variation Genome-wide association studies Genomes Genomics Genotype & phenotype Heritability Humans Kidney diseases Kidney Diseases, Cystic - genetics Kidney, Cystic Male Medical prognosis Nucleotide sequencing Polycystic kidney Rare diseases Receptors, Cell Surface Risk factors Statistical analysis Statistics Survival analysis Whole Genome Sequencing |
Title | Quantifying variant contributions in cystic kidney disease using national-scale whole-genome sequencing |
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