The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10414651" target="_blank" >RIV/00216208:11110/20:10414651 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/20:10414651
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=qQb.S8dH5j" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=qQb.S8dH5j</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-020-15383-w" target="_blank" >10.1038/s41467-020-15383-w</a>
Alternative languages
Result language
angličtina
Original language name
The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
Original language description
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 x 10(-12)) and IRF4 (rs9405192, OR = 1.29, P = 1.4 x 10(-14)), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 x 10(-103)) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 x 10(-49)), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 x 10(-93)), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 x 10(-23) and OR = 3.39, P = 5.2 x 10(-82), respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
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
30217 - Urology and nephrology
Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications [online]
ISSN
2041-1723
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
18
Pages from-to
1600
UT code for WoS article
000563559600001
EID of the result in the Scopus database
2-s2.0-85082558400