A catalog of genetic loci associated with kidney function from analyses of a million individuals
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication ( n = 1,046,070), we identified 264 associated...
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| Veröffentlicht in: | Nature genetics 2019-06, Vol.51 (6), p.957-972 |
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| creator | Wuttke, Matthias Tin, Adrienne Chai, Jin-Fang Tayo, Bamidele O. Fuchsberger, Christian Xu, Yizhe Yu, Zhi Akiyama, Masato Ahluwalia, Tarunveer S. Amin, Najaf Boissel, Mathilde Boutin, Thibaud S. Brenner, Hermann Campbell, Archie Cusi, Daniele Daw, E. Warwick de Borst, Martin H. Delgado, Graciela Dorajoo, Rajkumar Elliott, Paul Endlich, Karlhans Franco, Oscar H. Franke, Andre Freitag-Wolf, Sandra Froguel, Philippe Gaziano, J. Michael Gieger, Christian Gögele, Martin Gudbjartsson, Daniel F. Gudnason, Vilmundur Haller, Toomas Hicks, Andrew A. Hofer, Edith Ingelsson, Erik Jaddoe, Vincent W. V. Jakobsdottir, Johanna Jonas, Jost B. Joshi, Peter K. Jung, Bettina Kerr, Shona M. Kooner, Jaspal S. Körner, Antje Kovacs, Peter Krajcoviechova, Alena Krämer, Bernhard K. Kuokkanen, Mikko Langefeld, Carl D. Lieb, Wolfgang Lim, Su-Chi Loos, Ruth J. F. Lucae, Susanne Martins, Jade Matsuda, Koichi Milaneschi, Yuri Miliku, Kozeta Montgomery, Grant W. Nolte, Ilja M. Noordam, Raymond Orho-Melander, Marju Palsson, Runolfur Perola, Markus Pirastu, Mario Podgornaia, Anna I. Ponte, Belen Pramstaller, Peter P. Prins, Bram P. Raffield, Laura M. Ridker, Paul M. Roberts, David J. Rudan, Igor Saba, Yasaman Saum, Kai-Uwe Schöttker, Ben Smith, Albert V. Smith, Blair H. Taylor, Kent D. Thomsen, Hauke Toniolo, Daniela Tönjes, Anke van Dam, Rob M. Verweij, Niek Völker, Uwe Wallentin, Lars Waterworth, Dawn M. White, Harvey Wild, Sarah H. Wilson, James F. Yerges-Armstrong, Laura M. Bochud, Murielle Wilson, James G. Parsa, Afshin Chasman, Daniel I. Pendergrass, Sarah A. Sim, Xueling Böger, Carsten A. Okada, Yukinori Hung, Adriana M. Scholz, Markus Köttgen, Anna Pattaro, Cristian |
| description | Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (
n
= 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (
n
= 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease. |
| doi_str_mv | 10.1038/s41588-019-0407-x |
| format | Article |
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Warwick ; de Borst, Martin H. ; Delgado, Graciela ; Dorajoo, Rajkumar ; Elliott, Paul ; Endlich, Karlhans ; Franco, Oscar H. ; Franke, Andre ; Freitag-Wolf, Sandra ; Froguel, Philippe ; Gaziano, J. Michael ; Gieger, Christian ; Gögele, Martin ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hicks, Andrew A. ; Hofer, Edith ; Ingelsson, Erik ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Jung, Bettina ; Kerr, Shona M. ; Kooner, Jaspal S. ; Körner, Antje ; Kovacs, Peter ; Krajcoviechova, Alena ; Krämer, Bernhard K. ; Kuokkanen, Mikko ; Langefeld, Carl D. ; Lieb, Wolfgang ; Lim, Su-Chi ; Loos, Ruth J. F. ; Lucae, Susanne ; Martins, Jade ; Matsuda, Koichi ; Milaneschi, Yuri ; Miliku, Kozeta ; Montgomery, Grant W. ; Nolte, Ilja M. ; Noordam, Raymond ; Orho-Melander, Marju ; Palsson, Runolfur ; Perola, Markus ; Pirastu, Mario ; Podgornaia, Anna I. ; Ponte, Belen ; Pramstaller, Peter P. ; Prins, Bram P. ; Raffield, Laura M. ; Ridker, Paul M. ; Roberts, David J. ; Rudan, Igor ; Saba, Yasaman ; Saum, Kai-Uwe ; Schöttker, Ben ; Smith, Albert V. ; Smith, Blair H. ; Taylor, Kent D. ; Thomsen, Hauke ; Toniolo, Daniela ; Tönjes, Anke ; van Dam, Rob M. ; Verweij, Niek ; Völker, Uwe ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey ; Wild, Sarah H. ; Wilson, James F. ; Yerges-Armstrong, Laura M. ; Bochud, Murielle ; Wilson, James G. ; Parsa, Afshin ; Chasman, Daniel I. ; Pendergrass, Sarah A. ; Sim, Xueling ; Böger, Carsten A. ; Okada, Yukinori ; Hung, Adriana M. ; Scholz, Markus ; Köttgen, Anna ; Pattaro, Cristian</creator><creatorcontrib>Wuttke, Matthias ; Tin, Adrienne ; Chai, Jin-Fang ; Tayo, Bamidele O. ; Fuchsberger, Christian ; Xu, Yizhe ; Yu, Zhi ; Akiyama, Masato ; Ahluwalia, Tarunveer S. ; Amin, Najaf ; Boissel, Mathilde ; Boutin, Thibaud S. ; Brenner, Hermann ; Campbell, Archie ; Cusi, Daniele ; Daw, E. Warwick ; de Borst, Martin H. ; Delgado, Graciela ; Dorajoo, Rajkumar ; Elliott, Paul ; Endlich, Karlhans ; Franco, Oscar H. ; Franke, Andre ; Freitag-Wolf, Sandra ; Froguel, Philippe ; Gaziano, J. Michael ; Gieger, Christian ; Gögele, Martin ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hicks, Andrew A. ; Hofer, Edith ; Ingelsson, Erik ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Jung, Bettina ; Kerr, Shona M. ; Kooner, Jaspal S. ; Körner, Antje ; Kovacs, Peter ; Krajcoviechova, Alena ; Krämer, Bernhard K. ; Kuokkanen, Mikko ; Langefeld, Carl D. ; Lieb, Wolfgang ; Lim, Su-Chi ; Loos, Ruth J. F. ; Lucae, Susanne ; Martins, Jade ; Matsuda, Koichi ; Milaneschi, Yuri ; Miliku, Kozeta ; Montgomery, Grant W. ; Nolte, Ilja M. ; Noordam, Raymond ; Orho-Melander, Marju ; Palsson, Runolfur ; Perola, Markus ; Pirastu, Mario ; Podgornaia, Anna I. ; Ponte, Belen ; Pramstaller, Peter P. ; Prins, Bram P. ; Raffield, Laura M. ; Ridker, Paul M. ; Roberts, David J. ; Rudan, Igor ; Saba, Yasaman ; Saum, Kai-Uwe ; Schöttker, Ben ; Smith, Albert V. ; Smith, Blair H. ; Taylor, Kent D. ; Thomsen, Hauke ; Toniolo, Daniela ; Tönjes, Anke ; van Dam, Rob M. ; Verweij, Niek ; Völker, Uwe ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey ; Wild, Sarah H. ; Wilson, James F. ; Yerges-Armstrong, Laura M. ; Bochud, Murielle ; Wilson, James G. ; Parsa, Afshin ; Chasman, Daniel I. ; Pendergrass, Sarah A. ; Sim, Xueling ; Böger, Carsten A. ; Okada, Yukinori ; Hung, Adriana M. ; Scholz, Markus ; Köttgen, Anna ; Pattaro, Cristian ; V. A. Million Veteran Program ; Lifelines Cohort Study</creatorcontrib><description>Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (
n
= 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (
n
= 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.</description><identifier>ISSN: 1061-4036</identifier><identifier>ISSN: 1546-1718</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/s41588-019-0407-x</identifier><identifier>PMID: 31152163</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>45/43 ; 631/208 ; 631/208/205 ; 631/208/205/2138 ; 631/208/457 ; Agriculture ; Analysis ; Animal Genetics and Genomics ; Animal models ; Basic Medicine ; Bioinformatics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cardiovascular disease ; Chromosome Mapping ; Chronic kidney failure ; Diagnosis ; Epidermal growth factor receptors ; Gene expression ; Gene Function ; Gene loci ; Gene mapping ; Genes ; Genetic aspects ; Genetic Association Studies - methods ; Genetic markers ; Genetic Predisposition to Disease ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Glomerular Filtration Rate ; Health and Welfare ; Human Genetics ; Human tissues ; Humans ; Hälsa och välfärd ; Identification and classification ; Inheritance Patterns ; Kidney diseases ; Kidney Function Tests ; Kidneys ; Life Sciences ; Mapping ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Meta-analysis ; Metabolism ; Phenotype ; Phenotypes ; Polymorphism, Single Nucleotide ; Population ; Public health ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Renal Insufficiency, Chronic - genetics ; Renal Insufficiency, Chronic - physiopathology ; Renal Insufficiency, Chronic - urine ; Studies ; Urea ; Uromodulin - urine ; White People</subject><ispartof>Nature genetics, 2019-06, Vol.51 (6), p.957-972</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2019</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2019</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c819t-c591c40f24047fb5bf82460d2b2e9f8b837e152f4a42973cf19bccb25f7b42393</citedby><cites>FETCH-LOGICAL-c819t-c591c40f24047fb5bf82460d2b2e9f8b837e152f4a42973cf19bccb25f7b42393</cites><orcidid>0000-0003-1942-5845 ; 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A. Million Veteran Program</creatorcontrib><creatorcontrib>Lifelines Cohort Study</creatorcontrib><title>A catalog of genetic loci associated with kidney function from analyses of a million individuals</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (
n
= 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (
n
= 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.</description><subject>45/43</subject><subject>631/208</subject><subject>631/208/205</subject><subject>631/208/205/2138</subject><subject>631/208/457</subject><subject>Agriculture</subject><subject>Analysis</subject><subject>Animal Genetics and Genomics</subject><subject>Animal models</subject><subject>Basic Medicine</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cardiovascular disease</subject><subject>Chromosome Mapping</subject><subject>Chronic kidney failure</subject><subject>Diagnosis</subject><subject>Epidermal growth factor receptors</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>Gene loci</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies - methods</subject><subject>Genetic markers</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Glomerular Filtration Rate</subject><subject>Health and Welfare</subject><subject>Human Genetics</subject><subject>Human tissues</subject><subject>Humans</subject><subject>Hälsa och välfärd</subject><subject>Identification and classification</subject><subject>Inheritance Patterns</subject><subject>Kidney diseases</subject><subject>Kidney Function Tests</subject><subject>Kidneys</subject><subject>Life Sciences</subject><subject>Mapping</subject><subject>Medical and Health Sciences</subject><subject>Medical Genetics</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicinsk genetik</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>Meta-analysis</subject><subject>Metabolism</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Public health</subject><subject>Quantitative Trait Loci</subject><subject>Quantitative Trait, Heritable</subject><subject>Renal Insufficiency, Chronic - genetics</subject><subject>Renal Insufficiency, Chronic - physiopathology</subject><subject>Renal Insufficiency, Chronic - urine</subject><subject>Studies</subject><subject>Urea</subject><subject>Uromodulin - urine</subject><subject>White People</subject><issn>1061-4036</issn><issn>1546-1718</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>D8T</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwANygSFxVkOJTEvum0qocWmmlShx6a2zHzrpN4iVOttu3Z6JdWhaxgljWWOPv_-2MNUnyEqMTjCh_FxnOOc8QFhliqMzWj5JDnLMiwyXmj2GNCpwxRIuD5FmM1whhxhB_mhxQjHOCC3qYfJ-lRg2qCXUaXFrbzg7epE0wPlUxQlCDrdJbPyzSG1919i51Y2cGH7rU9aFNVaeau2jjpFZp65tm2vJd5Ve-GlUTnydPHAT7YhuPkm8fP3w9O8_ml58uzmbzzHAshszkAhuGHGGIlU7n2nHCClQRTaxwXHNaWrizY4oRUVLjsNDGaJK7UjNCBT1Kso1vvLXLUctl71vV38mgvNymbmBlJSsFlA34-V6-GZcwNcxJQOEmmmoidV4iyQTlUjtFZEWUwaoQlSomu7d77d77q5kMfS3HEcxKQSngb_6NV4AjgqZ_O93QgLa2MrYbetXsiHZ3Or-QdVjJohAcPjA43hgs_pCdz-ZyyiGW05yX-QoD-3p7WB9-jDYO8jqMPTxzlITQAlMscvJA1aqx0ncuwMGm9dHIGRhRjoq8AOrkLxSMyrbehM46D_kdwfGOAJjBrodajTHKiy-f_5-9vNpl8YY1fYixt-6-ChjJqZfkppck9JKcekmuQfPq96rfK341DwBk-4iw1dW2f6jUftefAjooFg</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Wuttke, Matthias</creator><creator>Tin, Adrienne</creator><creator>Chai, Jin-Fang</creator><creator>Tayo, Bamidele O.</creator><creator>Fuchsberger, Christian</creator><creator>Xu, Yizhe</creator><creator>Yu, Zhi</creator><creator>Akiyama, Masato</creator><creator>Ahluwalia, Tarunveer S.</creator><creator>Amin, Najaf</creator><creator>Boissel, Mathilde</creator><creator>Boutin, Thibaud S.</creator><creator>Brenner, Hermann</creator><creator>Campbell, Archie</creator><creator>Cusi, Daniele</creator><creator>Daw, E. 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catalog of genetic loci associated with kidney function from analyses of a million individuals</title><author>Wuttke, Matthias ; Tin, Adrienne ; Chai, Jin-Fang ; Tayo, Bamidele O. ; Fuchsberger, Christian ; Xu, Yizhe ; Yu, Zhi ; Akiyama, Masato ; Ahluwalia, Tarunveer S. ; Amin, Najaf ; Boissel, Mathilde ; Boutin, Thibaud S. ; Brenner, Hermann ; Campbell, Archie ; Cusi, Daniele ; Daw, E. Warwick ; de Borst, Martin H. ; Delgado, Graciela ; Dorajoo, Rajkumar ; Elliott, Paul ; Endlich, Karlhans ; Franco, Oscar H. ; Franke, Andre ; Freitag-Wolf, Sandra ; Froguel, Philippe ; Gaziano, J. Michael ; Gieger, Christian ; Gögele, Martin ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hicks, Andrew A. ; Hofer, Edith ; Ingelsson, Erik ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Jung, Bettina ; Kerr, Shona M. ; Kooner, Jaspal S. ; Körner, Antje ; Kovacs, Peter ; Krajcoviechova, Alena ; Krämer, Bernhard K. ; Kuokkanen, Mikko ; Langefeld, Carl D. ; Lieb, Wolfgang ; Lim, Su-Chi ; Loos, Ruth J. F. ; Lucae, Susanne ; Martins, Jade ; Matsuda, Koichi ; Milaneschi, Yuri ; Miliku, Kozeta ; Montgomery, Grant W. ; Nolte, Ilja M. ; Noordam, Raymond ; Orho-Melander, Marju ; Palsson, Runolfur ; Perola, Markus ; Pirastu, Mario ; Podgornaia, Anna I. ; Ponte, Belen ; Pramstaller, Peter P. ; Prins, Bram P. ; Raffield, Laura M. ; Ridker, Paul M. ; Roberts, David J. ; Rudan, Igor ; Saba, Yasaman ; Saum, Kai-Uwe ; Schöttker, Ben ; Smith, Albert V. ; Smith, Blair H. ; Taylor, Kent D. ; Thomsen, Hauke ; Toniolo, Daniela ; Tönjes, Anke ; van Dam, Rob M. ; Verweij, Niek ; Völker, Uwe ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey ; Wild, Sarah H. ; Wilson, James F. ; Yerges-Armstrong, Laura M. ; Bochud, Murielle ; Wilson, James G. ; Parsa, Afshin ; Chasman, Daniel I. ; Pendergrass, Sarah A. ; Sim, Xueling ; Böger, Carsten A. ; Okada, Yukinori ; Hung, Adriana M. ; Scholz, Markus ; Köttgen, Anna ; Pattaro, Cristian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c819t-c591c40f24047fb5bf82460d2b2e9f8b837e152f4a42973cf19bccb25f7b42393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>45/43</topic><topic>631/208</topic><topic>631/208/205</topic><topic>631/208/205/2138</topic><topic>631/208/457</topic><topic>Agriculture</topic><topic>Analysis</topic><topic>Animal Genetics and Genomics</topic><topic>Animal models</topic><topic>Basic Medicine</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cardiovascular disease</topic><topic>Chromosome Mapping</topic><topic>Chronic kidney failure</topic><topic>Diagnosis</topic><topic>Epidermal growth factor receptors</topic><topic>Gene expression</topic><topic>Gene Function</topic><topic>Gene loci</topic><topic>Gene mapping</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies - methods</topic><topic>Genetic markers</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Glomerular Filtration Rate</topic><topic>Health and Welfare</topic><topic>Human Genetics</topic><topic>Human tissues</topic><topic>Humans</topic><topic>Hälsa och välfärd</topic><topic>Identification and classification</topic><topic>Inheritance Patterns</topic><topic>Kidney diseases</topic><topic>Kidney Function Tests</topic><topic>Kidneys</topic><topic>Life Sciences</topic><topic>Mapping</topic><topic>Medical and Health Sciences</topic><topic>Medical Genetics</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicinsk genetik</topic><topic>Medicinska och farmaceutiska grundvetenskaper</topic><topic>Meta-analysis</topic><topic>Metabolism</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Public health</topic><topic>Quantitative Trait Loci</topic><topic>Quantitative Trait, Heritable</topic><topic>Renal Insufficiency, Chronic - genetics</topic><topic>Renal Insufficiency, Chronic - physiopathology</topic><topic>Renal Insufficiency, Chronic - urine</topic><topic>Studies</topic><topic>Urea</topic><topic>Uromodulin - urine</topic><topic>White People</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wuttke, Matthias</creatorcontrib><creatorcontrib>Tin, Adrienne</creatorcontrib><creatorcontrib>Chai, Jin-Fang</creatorcontrib><creatorcontrib>Tayo, Bamidele O.</creatorcontrib><creatorcontrib>Fuchsberger, Christian</creatorcontrib><creatorcontrib>Xu, Yizhe</creatorcontrib><creatorcontrib>Yu, Zhi</creatorcontrib><creatorcontrib>Akiyama, Masato</creatorcontrib><creatorcontrib>Ahluwalia, Tarunveer S.</creatorcontrib><creatorcontrib>Amin, Najaf</creatorcontrib><creatorcontrib>Boissel, Mathilde</creatorcontrib><creatorcontrib>Boutin, Thibaud S.</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Campbell, Archie</creatorcontrib><creatorcontrib>Cusi, Daniele</creatorcontrib><creatorcontrib>Daw, E. 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Warwick</au><au>de Borst, Martin H.</au><au>Delgado, Graciela</au><au>Dorajoo, Rajkumar</au><au>Elliott, Paul</au><au>Endlich, Karlhans</au><au>Franco, Oscar H.</au><au>Franke, Andre</au><au>Freitag-Wolf, Sandra</au><au>Froguel, Philippe</au><au>Gaziano, J. Michael</au><au>Gieger, Christian</au><au>Gögele, Martin</au><au>Gudbjartsson, Daniel F.</au><au>Gudnason, Vilmundur</au><au>Haller, Toomas</au><au>Hicks, Andrew A.</au><au>Hofer, Edith</au><au>Ingelsson, Erik</au><au>Jaddoe, Vincent W. V.</au><au>Jakobsdottir, Johanna</au><au>Jonas, Jost B.</au><au>Joshi, Peter K.</au><au>Jung, Bettina</au><au>Kerr, Shona M.</au><au>Kooner, Jaspal S.</au><au>Körner, Antje</au><au>Kovacs, Peter</au><au>Krajcoviechova, Alena</au><au>Krämer, Bernhard K.</au><au>Kuokkanen, Mikko</au><au>Langefeld, Carl D.</au><au>Lieb, Wolfgang</au><au>Lim, Su-Chi</au><au>Loos, Ruth J. F.</au><au>Lucae, Susanne</au><au>Martins, Jade</au><au>Matsuda, Koichi</au><au>Milaneschi, Yuri</au><au>Miliku, Kozeta</au><au>Montgomery, Grant W.</au><au>Nolte, Ilja M.</au><au>Noordam, Raymond</au><au>Orho-Melander, Marju</au><au>Palsson, Runolfur</au><au>Perola, Markus</au><au>Pirastu, Mario</au><au>Podgornaia, Anna I.</au><au>Ponte, Belen</au><au>Pramstaller, Peter P.</au><au>Prins, Bram P.</au><au>Raffield, Laura M.</au><au>Ridker, Paul M.</au><au>Roberts, David J.</au><au>Rudan, Igor</au><au>Saba, Yasaman</au><au>Saum, Kai-Uwe</au><au>Schöttker, Ben</au><au>Smith, Albert V.</au><au>Smith, Blair H.</au><au>Taylor, Kent D.</au><au>Thomsen, Hauke</au><au>Toniolo, Daniela</au><au>Tönjes, Anke</au><au>van Dam, Rob M.</au><au>Verweij, Niek</au><au>Völker, Uwe</au><au>Wallentin, Lars</au><au>Waterworth, Dawn M.</au><au>White, Harvey</au><au>Wild, Sarah H.</au><au>Wilson, James F.</au><au>Yerges-Armstrong, Laura M.</au><au>Bochud, Murielle</au><au>Wilson, James G.</au><au>Parsa, Afshin</au><au>Chasman, Daniel I.</au><au>Pendergrass, Sarah A.</au><au>Sim, Xueling</au><au>Böger, Carsten A.</au><au>Okada, Yukinori</au><au>Hung, Adriana M.</au><au>Scholz, Markus</au><au>Köttgen, Anna</au><au>Pattaro, Cristian</au><aucorp>V. A. Million Veteran Program</aucorp><aucorp>Lifelines Cohort Study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A catalog of genetic loci associated with kidney function from analyses of a million individuals</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>51</volume><issue>6</issue><spage>957</spage><epage>972</epage><pages>957-972</pages><issn>1061-4036</issn><issn>1546-1718</issn><eissn>1546-1718</eissn><abstract>Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (
n
= 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (
n
= 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.</abstract><cop>New York</cop><pub>Nature Publishing Group 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| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2019-06, Vol.51 (6), p.957-972 |
| issn | 1061-4036 1546-1718 1546-1718 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_479415 |
| source | MEDLINE; Nature; SWEPUB Freely available online; SpringerLink Journals - AutoHoldings |
| subjects | 45/43 631/208 631/208/205 631/208/205/2138 631/208/457 Agriculture Analysis Animal Genetics and Genomics Animal models Basic Medicine Bioinformatics Biomedical and Life Sciences Biomedicine Cancer Research Cardiovascular disease Chromosome Mapping Chronic kidney failure Diagnosis Epidermal growth factor receptors Gene expression Gene Function Gene loci Gene mapping Genes Genetic aspects Genetic Association Studies - methods Genetic markers Genetic Predisposition to Disease Genetics Genome-wide association studies Genome-Wide Association Study Genomes Glomerular Filtration Rate Health and Welfare Human Genetics Human tissues Humans Hälsa och välfärd Identification and classification Inheritance Patterns Kidney diseases Kidney Function Tests Kidneys Life Sciences Mapping Medical and Health Sciences Medical Genetics Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Meta-analysis Metabolism Phenotype Phenotypes Polymorphism, Single Nucleotide Population Public health Quantitative Trait Loci Quantitative Trait, Heritable Renal Insufficiency, Chronic - genetics Renal Insufficiency, Chronic - physiopathology Renal Insufficiency, Chronic - urine Studies Urea Uromodulin - urine White People |
| title | A catalog of genetic loci associated with kidney function from analyses of a million individuals |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T23%3A49%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20catalog%20of%20genetic%20loci%20associated%20with%20kidney%20function%20from%20analyses%20of%20a%20million%20individuals&rft.jtitle=Nature%20genetics&rft.au=Wuttke,%20Matthias&rft.aucorp=V.%20A.%20Million%20Veteran%20Program&rft.date=2019-06-01&rft.volume=51&rft.issue=6&rft.spage=957&rft.epage=972&rft.pages=957-972&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/s41588-019-0407-x&rft_dat=%3Cgale_swepu%3EA587380656%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2236131952&rft_id=info:pmid/31152163&rft_galeid=A587380656&rfr_iscdi=true |