Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F24%3A00079770" target="_blank" >RIV/00209805:_____/24:00079770 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10479734 RIV/00216208:11130/24:10479734 RIV/00064203:_____/24:10479734

Výsledek na webu

<a href="https://www.nature.com/articles/s41588-024-01725-7" target="_blank" >https://www.nature.com/articles/s41588-024-01725-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-024-01725-7" target="_blank" >10.1038/s41588-024-01725-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

Popis výsledku v původním jazyce

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3&apos; untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

Název v anglickém jazyce

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions

Popis výsledku anglicky

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3&apos; untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

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

56

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

809-818

Kód UT WoS článku

001253202700001

EID výsledku v databázi Scopus

2-s2.0-85191307064