Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F22%3A00079085" target="_blank" >RIV/00209805:_____/22:00079085 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41375-022-01711-0" target="_blank" >https://www.nature.com/articles/s41375-022-01711-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41375-022-01711-0" target="_blank" >10.1038/s41375-022-01711-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Popis výsledku v původním jazyce

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P &lt; 5 x 10(-8)) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 x 10(-9)). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P &lt; 5 x 10(-8)), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

Název v anglickém jazyce

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Popis výsledku anglicky

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P &lt; 5 x 10(-8)) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 x 10(-9)). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P &lt; 5 x 10(-8)), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

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

2022

Kód důvěrnosti údajů

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

Název periodika

LEUKEMIA

ISSN

0887-6924

e-ISSN

1476-5551

Svazek periodika

36

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

2835-2844

Kód UT WoS článku

000871170900001

EID výsledku v databázi Scopus

2-s2.0-85140325134