Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F19%3AN0000025" target="_blank" >RIV/00064190:_____/19:N0000025 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/19:10400902
Result on the web
<a href="http://dx.doi.org/10.1038/s41588-019-0504-x" target="_blank" >http://dx.doi.org/10.1038/s41588-019-0504-x</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41588-019-0504-x" target="_blank" >10.1038/s41588-019-0504-x</a>
Alternative languages
Result language
angličtina
Original language name
Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
Original language description
Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
—
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
NATURE GENETICS
ISSN
1061-4036
e-ISSN
1546-1718
Volume of the periodical
51
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
1459-1474
UT code for WoS article
000489016400010
EID of the result in the Scopus database
2-s2.0-85074209366