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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Gorski Mathias; Rasheed Humaira; Teumer Alexander; Thomas Laurent F.; Graham Sarah E.; Sveinbjornsson Gardar; Winkler Thomas W.; Günther Felix; Stark Klaus J.; Chai Jin-Fang; Tayo Bamidele O.; Wuttke Matthias; Li Yong; Tin Adrienne; Ahluwalia Tarunveer S.; Ärnlöv Johan; Åsvold Bjørn Olav; Bakker Stephan J.L.; Banas Bernhard; Bansal Nisha; Biggs Mary L.; Biino Ginevra; Böhnke Michael; Boerwinkle Eric; Bottinger Erwin P.; Brenner Hermann; Brumpton Ben; Carroll Robert J.; Chaker Layal; Chalmers John; Chee Miao-Li; Chee Miao-Ling; Cheng Ching-Yu; Y.Chu Audrey; Ciullo Marina; Cocca Massimiliano; Cook James P.; Coresh Josef; Cusi Daniele; de Borst Martin H.; Degenhardt Frauke; Eckardt Kai-Uwe; Endlich Karlhans; Evans Michele K.; Feitosa Mary F.; Franke Andre; Freitag-Wolf Sandra; Fuchsberger Christian; Gampawar Piyush; Gansevoort Ron T.; Ghanbari Mohsen; Ghasemi Sahar; Giedraitis Vilmantas; Gieger Christian; Gudbjartsson Daniel F.; Hallan Stein; Hamet Pavel; Hishida Asahi; Ho Kevin; Hofer Edith; Holleczek Bernd; Holm Hilma; Hoppmann Anselm; Horn Katrin; Hutri-Kähönen Nina; Hveem Kristian; Hwang Shih-Jen; Ikram M. Arfan; Josyula Navya Shilpa; Jung Bettina; Kähönen Mika; Karabegović Irma; Khor Chiea-Chuen; Koenig Wolfgang; Kramer Holly; Krämer Bernhard K.; Kühnel Brigitte; Kuusisto Johanna; Laakso Markku; Lange Leslie A.; Lehtimäki Terho; Li Man; Lieb Wolfgang; Lind Lars; Lindgren Cecilia M.; Loos Ruth J.F.; Lukas Mary Ann; Lyytikäinen Leo-Pekka; Mahajan Anubha; Matias-Garcia Pamela R.; Meisinger Christa; Meitinger Thomas; Melander Olle; Milaneschi Yuri; Mishra Pashupati P.; Mononen Nina; Morris Andrew P.; Mychaleckyj Josyf C.; Nadkarni Girish N.; Naito Mariko; Nakatochi Masahiro; Nalls Mike A.; Nauck Matthias; Nikus Kjell; Ning Boting; Nolte Ilja M.; Nutile Teresa; O’Donoghue Michelle L.; O'Connell Jeffrey; Olafsson Isleifur; Orho-Melander Marju; Parsa Afshin; Pendergrass Sarah A.; Penninx Brenda W.J.H.; Pirastu Mario; Preuss Michael H.; Psaty Bruce M.; M.Raffield Laura; Raitakari Olli T.; Rheinberger Myriam; Rice Kenneth M.; Rizzi Federica; Rosenkranz Alexander R.; Rossing Peter; Rotter Jerome I.; Ruggiero Daniela; Ryan Kathleen A.; Sabanayagam Charumathi; Salvi Erika; Schmidt Helena; Schmidt Reinhold; Scholz Markus; Schöttker Ben; Schulz Christina-Alexandra; Sedaghat Sanaz; Shaffer Christian M.; Sieber Karsten B.; Sim Xueling; Sims Mario; Snieder Harold; Stanzick Kira J.; Thorsteinsdottir Unnur; Stocker Hannah; Strauch Konstantin; Stringham Heather M.; Sulem Patrick; Szymczak Silke; Taylor Kent D.; Thio Chris H.L.; Tremblay Johanne; Vaccargiu Simona; van der Harst Pim; van der Most Peter J.; Verweij Niek; Völker Uwe; Wakai Kenji; Waldenberger Melanie; Wallentin Lars; Wallner Stefan; Wang Judy; Waterworth Dawn M.; White Harvey D.; Willer Cristen J.; Wong Tien-Yin; Woodward Mark; Yang Qiong; Yerges-Armstrong Laura M.; Zimmermann Martina; Zonderman Alan B.; Bergler Tobias; Stefansson Kari; Böger Carsten A.; Pattaro Cristian; Köttgen Anna; Kronenberg Florian; Heid Iris M.; Lifelines Cohort Study

Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Gorski Mathias
Rasheed Humaira
Teumer Alexander
Thomas Laurent F.
Graham Sarah E.
Sveinbjornsson Gardar
Winkler Thomas W.
Günther Felix
Stark Klaus J.
Chai Jin-Fang
Tayo Bamidele O.
Wuttke Matthias
Li Yong
Tin Adrienne
Ahluwalia Tarunveer S.
Ärnlöv Johan
Åsvold Bjørn Olav
Bakker Stephan J.L.
Banas Bernhard
Bansal Nisha
Biggs Mary L.
Biino Ginevra
Böhnke Michael
Boerwinkle Eric
Bottinger Erwin P.
Brenner Hermann
Brumpton Ben
Carroll Robert J.
Chaker Layal
Chalmers John
Chee Miao-Li
Chee Miao-Ling
Cheng Ching-Yu
Y.Chu Audrey
Ciullo Marina
Cocca Massimiliano
Cook James P.
Coresh Josef
Cusi Daniele
de Borst Martin H.
Degenhardt Frauke
Eckardt Kai-Uwe
Endlich Karlhans
Evans Michele K.
Feitosa Mary F.
Franke Andre
Freitag-Wolf Sandra
Fuchsberger Christian
Gampawar Piyush
Gansevoort Ron T.
Ghanbari Mohsen
Ghasemi Sahar
Giedraitis Vilmantas
Gieger Christian
Gudbjartsson Daniel F.
Hallan Stein
Hamet Pavel
Hishida Asahi
Ho Kevin
Hofer Edith
Holleczek Bernd
Holm Hilma
Hoppmann Anselm
Horn Katrin
Hutri-Kähönen Nina
Hveem Kristian
Hwang Shih-Jen
Ikram M. Arfan
Josyula Navya Shilpa
Jung Bettina
Kähönen Mika
Karabegović Irma
Khor Chiea-Chuen
Koenig Wolfgang
Kramer Holly
Krämer Bernhard K.
Kühnel Brigitte
Kuusisto Johanna
Laakso Markku
Lange Leslie A.
Lehtimäki Terho
Li Man
Lieb Wolfgang
Lind Lars
Lindgren Cecilia M.
Loos Ruth J.F.
Lukas Mary Ann
Lyytikäinen Leo-Pekka
Mahajan Anubha
Matias-Garcia Pamela R.
Meisinger Christa
Meitinger Thomas
Melander Olle
Milaneschi Yuri
Mishra Pashupati P.
Mononen Nina
Morris Andrew P.
Mychaleckyj Josyf C.
Nadkarni Girish N.
Naito Mariko
Nakatochi Masahiro
Nalls Mike A.
Nauck Matthias
Nikus Kjell
Ning Boting
Nolte Ilja M.
Nutile Teresa
O’Donoghue Michelle L.
O'Connell Jeffrey
Olafsson Isleifur
Orho-Melander Marju
Parsa Afshin
Pendergrass Sarah A.
Penninx Brenda W.J.H.
Pirastu Mario
Preuss Michael H.
Psaty Bruce M.
M.Raffield Laura
Raitakari Olli T.
Rheinberger Myriam
Rice Kenneth M.
Rizzi Federica
Rosenkranz Alexander R.
Rossing Peter
Rotter Jerome I.
Ruggiero Daniela
Ryan Kathleen A.
Sabanayagam Charumathi
Salvi Erika
Schmidt Helena
Schmidt Reinhold
Scholz Markus
Schöttker Ben
Schulz Christina-Alexandra
Sedaghat Sanaz
Shaffer Christian M.
Sieber Karsten B.
Sim Xueling
Sims Mario
Snieder Harold
Stanzick Kira J.
Thorsteinsdottir Unnur
Stocker Hannah
Strauch Konstantin
Stringham Heather M.
Sulem Patrick
Szymczak Silke
Taylor Kent D.
Thio Chris H.L.
Tremblay Johanne
Vaccargiu Simona
van der Harst Pim
van der Most Peter J.
Verweij Niek
Völker Uwe
Wakai Kenji
Waldenberger Melanie
Wallentin Lars
Wallner Stefan
Wang Judy
Waterworth Dawn M.
White Harvey D.
Willer Cristen J.
Wong Tien-Yin
Woodward Mark
Yang Qiong
Yerges-Armstrong Laura M.
Zimmermann Martina
Zonderman Alan B.
Bergler Tobias
Stefansson Kari
Böger Carsten A.
Pattaro Cristian
Köttgen Anna
Kronenberg Florian
Heid Iris M.
Lifelines Cohort Study
Katso/Avaa
1-s2.0-S0085253822004549-main.pdf (2.495Mb)
Lataukset: 

Elsevier
doi:10.1016/j.kint.2022.05.021
URI
https://doi.org/10.1016/j.kint.2022.05.021
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022091258784
Tiivistelmä

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.

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