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@ARTICLE{Gorski:164261,
author = {M. Gorski and B. Jung and Y. Li and P. R. Matias-Garcia and
M. Wuttke and S. Coassin and C. H. L. Thio and M. E. Kleber
and T. W. Winkler and V. Wanner and J.-F. Chai and A. Y. Chu
and M. Cocca and M. F. Feitosa and S. Ghasemi and A.
Hoppmann and K. Horn and M. Li and T. Nutile and M. Scholz
and K. B. Sieber and A. Teumer and A. Tin and J. Wang and B.
O. Tayo and T. S. Ahluwalia and P. Almgren and S. J. L.
Bakker and B. Banas and N. Bansal and M. L. Biggs and E.
Boerwinkle and E. P. Bottinger and H. Brenner$^*$ and R. J.
Carroll and J. Chalmers and M.-L. Chee and M.-L. Chee and
C.-Y. Cheng and J. Coresh and M. H. de Borst and F.
Degenhardt and K.-U. Eckardt and K. Endlich and A. Franke
and S. Freitag-Wolf and P. Gampawar and R. T. Gansevoort and
M. Ghanbari and C. Gieger and P. Hamet and K. Ho and E.
Hofer and B. Holleczek$^*$ and V. H. Xian Foo and N.
Hutri-Kähönen and S.-J. Hwang and M. A. Ikram and N. S.
Josyula and M. Kähönen and C.-C. Khor and W. Koenig and H.
Kramer and B. K. Krämer and B. Kühnel and L. A. Lange and
T. Lehtimäki and W. Lieb and R. J. F. Loos and M. A. Lukas
and L.-P. Lyytikäinen and C. Meisinger and T. Meitinger and
O. Melander and Y. Milaneschi and P. P. Mishra and N.
Mononen and J. C. Mychaleckyj and G. N. Nadkarni and M.
Nauck and K. Nikus and B. Ning and I. M. Nolte and M. L.
O'Donoghue and M. Orho-Melander and S. A. Pendergrass and B.
W. J. H. Penninx and M. H. Preuss and B. M. Psaty and L. M.
Raffield and O. T. Raitakari and R. Rettig and M.
Rheinberger and K. M. Rice and A. R. Rosenkranz and P.
Rossing and J. I. Rotter and C. Sabanayagam and H. Schmidt
and R. Schmidt and B. Schöttker$^*$ and C.-A. Schulz and S.
Sedaghat and C. M. Shaffer and K. Strauch and S. Szymczak
and K. D. Taylor and J. Tremblay and L. Chaker and P. van
der Harst and P. J. van der Most and N. Verweij and U.
Völker and M. Waldenberger and L. Wallentin and D. M.
Waterworth and H. D. White and J. G. Wilson and T.-Y. Wong
and M. Woodward and Q. Yang and M. Yasuda and L. M.
Yerges-Armstrong and Y. Zhang and H. Snieder and C. Wanner
and C. A. Böger and A. Köttgen and F. Kronenberg and C.
Pattaro and I. M. Heid},
collaboration = {L. c. study and R. G. Center},
title = {{M}eta-analysis uncovers genome-wide significant variants
for rapid kidney function decline.},
journal = {Kidney international},
volume = {99},
number = {4},
issn = {0085-2538},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2020-02347},
pages = {926-939},
year = {2021},
note = {2021 Apr;99(4):926-939},
abstract = {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/1.73m2/year or more ('Rapid3'; encompassing 34,874
cases, 107,090 controls) and eGFRcrea decline $25\%$ or more
and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those
with eGFRcrea 60 mL/min/1.73m2 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.},
cin = {C070},
ddc = {610},
cid = {I:(DE-He78)C070-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33137338},
doi = {10.1016/j.kint.2020.09.030},
url = {https://inrepo02.dkfz.de/record/164261},
}