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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
- Source :
- Kidney International, 102(3), 624-639. Nature Publishing Group, Kidney International, Gorski, M, Rasheed, H, Teumer, A, Thomas, L F, Graham, S E, Sveinbjornsson, G, Winkler, T W, Günther, F, Stark, K J, Chai, J-F, Tayo, B O, Wuttke, M, Li, Y, Tin, A, Ahluwalia, T S, Ärnlöv, J, Åsvold, B O, Bakker, S J L, Banas, B, Bansal, N, Biggs, M L, Biino, G, Böhnke, M, Boerwinkle, E, Bottinger, E P, Brenner, H, Brumpton, B, Carroll, R J, Chaker, L, Chalmers, J, Chee, M-L, Chee, M-L, Cheng, C-Y, Chu, A Y, Ciullo, M, Cocca, M, Cook, J P, Coresh, J, Cusi, D, de Borst, M H, Degenhardt, F, Eckardt, K-U, Endlich, K, Evans, M K, Feitosa, M F, Franke, A, Freitag-Wolf, S, Rossing, P & LifeLines Cohort Study 2022, ' Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies ', Kidney International, vol. 102, no. 3, pp. 624-639 . https://doi.org/10.1016/j.kint.2022.05.021, Kidney International, 102(3), 624-639. ELSEVIER SCIENCE INC, Lifelines Cohort Study 2022, ' Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies ', Kidney International, vol. 102, no. 3, pp. 624-639 . https://doi.org/10.1016/j.kint.2022.05.021, Kidney International, 102(3), 624-639. Elsevier Inc.
- Publication Year :
- 2022
-
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. publishedVersion
- Subjects :
- acute kidney injury, chronic kidney disease, diabetes, gene expression
610 Medizin
Kidney
Urologi och njurmedicin
Humans
Urology and Nephrology
ddc:610
Longitudinal Studies
Renal Insufficiency
Renal Insufficiency, Chronic
Medicinsk genetik
diabetes
Public Health, Global Health, Social Medicine and Epidemiology
Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
Cross-Sectional Studies
acute kidney injury
Genetic Loci
Nephrology
gene expression
N-Acetylgalactosaminyltransferases
3111 Biomedicine
Medical Genetics
chronic kidney disease
Genome-Wide Association Study
Glomerular Filtration Rate
Subjects
Details
- Language :
- English
- ISSN :
- 00852538
- Database :
- OpenAIRE
- Journal :
- Kidney International, 102(3), 624-639. Nature Publishing Group, Kidney International, Gorski, M, Rasheed, H, Teumer, A, Thomas, L F, Graham, S E, Sveinbjornsson, G, Winkler, T W, Günther, F, Stark, K J, Chai, J-F, Tayo, B O, Wuttke, M, Li, Y, Tin, A, Ahluwalia, T S, Ärnlöv, J, Åsvold, B O, Bakker, S J L, Banas, B, Bansal, N, Biggs, M L, Biino, G, Böhnke, M, Boerwinkle, E, Bottinger, E P, Brenner, H, Brumpton, B, Carroll, R J, Chaker, L, Chalmers, J, Chee, M-L, Chee, M-L, Cheng, C-Y, Chu, A Y, Ciullo, M, Cocca, M, Cook, J P, Coresh, J, Cusi, D, de Borst, M H, Degenhardt, F, Eckardt, K-U, Endlich, K, Evans, M K, Feitosa, M F, Franke, A, Freitag-Wolf, S, Rossing, P & LifeLines Cohort Study 2022, ' Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies ', Kidney International, vol. 102, no. 3, pp. 624-639 . https://doi.org/10.1016/j.kint.2022.05.021, Kidney International, 102(3), 624-639. ELSEVIER SCIENCE INC, Lifelines Cohort Study 2022, ' Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies ', Kidney International, vol. 102, no. 3, pp. 624-639 . https://doi.org/10.1016/j.kint.2022.05.021, Kidney International, 102(3), 624-639. Elsevier Inc.
- Accession number :
- edsair.doi.dedup.....5049919bcc0b895e4127e74847f93ef7