Student and Faculty Publications

Authors

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

Publication Date

9-1-2022

Journal

Kidney International

Abstract

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.

Keywords

Cross-Sectional Studies, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Longitudinal Studies, N-Acetylgalactosaminyltransferases, Renal Insufficiency, Renal Insufficiency, Chronic

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