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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.
Monday,2021-01-25 16:17 America/Los_Angeles — ecterry
| Title | Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Gorski, M, Jung, B, Li, Y, Matias-Garcia, PR, Wuttke, M, Coassin, S, Thio, CHL, Kleber, ME, Winkler, TW, Wanner, V, Chai, J-F, Chu, AY, Cocca, M, Feitosa, MF, Ghasemi, S, Hoppmann, A, Horn, K, Li, M, Nutile, T, Scholz, M, Sieber, KB, Teumer, A, Tin, A, Wang, J, Tayo, BO, Ahluwalia, TS, Almgren, P, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Boerwinkle, E, Bottinger, EP, Brenner, H, Carroll, RJ, Chalmers, J, Chee, M-L, Chee, M-L, Cheng, C-Y, Coresh, J, de Borst, MH, Degenhardt, F, Eckardt, K-U, Endlich, K, Franke, A, Freitag-Wolf, S, Gampawar, P, Gansevoort, RT, Ghanbari, M, Gieger, C, Hamet, P, Ho, K, Hofer, E, Holleczek, B, Foo, VHui Xian, Hutri-Kähönen, N, Hwang, S-J, Ikram, AM, Josyula, NShilpa, Kähönen, M, Khor, C-C, Koenig, W, Kramer, H, Krämer, BK, Kuhnel, B, Lange, LA, Lehtimäki, T, Lieb, W, Loos, RJF, Lukas, MAnn, Lyytikäinen, L-P, Meisinger, C, Meitinger, T, Melander, O, Milaneschi, Y, Mishra, PP, Mononen, N, Mychaleckyj, JC, Nadkarni, GN, Nauck, M, Nikus, K, Ning, B, Nolte, IM, O'Donoghue, ML, Orho-Melander, M, Pendergrass, SA, Penninx, BWJH, Preuss, MH, Psaty, BM, Raffield, LM, Raitakari, OT, Rettig, R, Rheinberger, M, Rice, KM, Rosenkranz, AR, Rossing, P, Rotter, JI, Sabanayagam, C, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, C-A, Sedaghat, S, Shaffer, CM, Strauch, K, Szymczak, S, Taylor, KD, Tremblay, J, Chaker, L, van der Harst, P, van der Most, PJ, Verweij, N, Völker, U, Waldenberger, M, Wallentin, L, Waterworth, DM, White, HD, Wilson, JG, Wong, T-Y, Woodward, M, Yang, Q, Yasuda, M, Yerges-Armstrong, LM, Zhang, Y, Snieder, H, Wanner, C, Böger, CA, Köttgen, A, Kronenberg, F, Pattaro, C, Heid, IM |
| Corporate/Institutional Authors | LifeLines Cohort Study,, Regeneron Genetics Center |
| Journal | Kidney Int |
| Date Published | 2020 Oct 30 |
| ISSN | 1523-1755 |
| Abstract | <p>Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m at follow-up among those with eGFRcrea 60 mL/min/1.73m or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.</p> |
| DOI | 10.1016/j.kint.2020.09.030 |
| Alternate Journal | Kidney Int |
| PubMed ID | 33137338 |
ePub date:
20/10