Dataset Information

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

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.

SUBMITTER: Gorski M

PROVIDER: S-EPMC10034922 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

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

Kidney international 20220616 3

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 34 ...[more]

PMID: 35716955

Similar Datasets

Project description:BackgroundEvidence linking chronic kidney disease (CKD) and sleep duration is inconsistent. This study examined whether sleep duration is associated with a long-term risk of kidney function decline.MethodsThis retrospective, longitudinal cohort study included 82 001 participants who visited a primary care centre in Japan. Participants were categorized into CKD risk groups and sleep duration categories according to their self-reported average nightly sleep duration. The relationship between average nightly sleep duration and the incidence of composite renal outcome comprised a ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline and a decline in eGFR to <15 mL/min/1.73 m² was evaluated.ResultsThe mean age and eGFR (±standard deviation) of the patient cohort were 45.8 (±12.4) years and 81.8 (±15.4) mL/min/1.73 m², respectively. A total of 41 891 participants (51.1%) were women. During the median follow-up of 5.1 years [interquartile range 2.2-9.6], 4214 (5.1%) participants achieved the composite renal outcome. Only the long and very long sleep durations (≥8 h/night) were associated with an increased incidence of the composite renal outcome compared with the reference duration (7 h/night) [adjusted odds ratio (OR) 1.22 and 1.44; 95% confidence interval (CI) 1.09-1.36 and 1.13-1.84, for long and very long sleep durations, respectively]. Furthermore, this association was significant for both long and very long sleep durations in the low CKD risk group but only for long sleep duration in the intermediate CKD risk group. The results of the sex-specific analysis showed that men had a decreased risk of achieving the composite renal outcome (OR 0.91; 95% CI 0.79-1.06), while there was an increased risk for women (OR 1.14; 95% CI 1.02-1.28).ConclusionsAverage sleep durations ≥8 h/night were associated with an increased incidence of poor renal outcomes over time. However, a longitudinal cohort study is required to confirm whether sleep duration can prevent poor renal outcomes.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets