A catalog of genetic loci associated with kidney function from analyses of a million individuals

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F19%3AN0000055" target="_blank" >RIV/00064190:_____/19:N0000055 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/19:10407623

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41588-019-0407-x" target="_blank" >http://dx.doi.org/10.1038/s41588-019-0407-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-019-0407-x" target="_blank" >10.1038/s41588-019-0407-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A catalog of genetic loci associated with kidney function from analyses of a million individuals

Popis výsledku v původním jazyce

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Název v anglickém jazyce

A catalog of genetic loci associated with kidney function from analyses of a million individuals

Popis výsledku anglicky

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

NATURE GENETICS

ISSN

1061-4036

e-ISSN

1546-1718

Svazek periodika

51

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

42

Strana od-do

957-1000

Kód UT WoS článku

000469996900008

EID výsledku v databázi Scopus

2-s2.0-85066607502