Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F21%3A00075224" target="_blank" >RIV/00159816:_____/21:00075224 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/21:10428372 RIV/00216208:11130/21:10428372

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-021-22491-8" target="_blank" >https://www.nature.com/articles/s41467-021-22491-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-021-22491-8" target="_blank" >10.1038/s41467-021-22491-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Popis výsledku v původním jazyce

Genetic discoveries of Alzheimer&apos;s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n=409,435 and validation size n=58,190). Here, we add six variants associated with Alzheimer&apos;s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer&apos;s disease patients in APOE 4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer&apos;s disease. Known genetic loci account for only a fraction of the genetic contribution to Alzheimer&apos;s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer&apos;s disease polygenic risk score.

Název v anglickém jazyce

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Popis výsledku anglicky

Genetic discoveries of Alzheimer&apos;s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n=409,435 and validation size n=58,190). Here, we add six variants associated with Alzheimer&apos;s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer&apos;s disease patients in APOE 4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer&apos;s disease. Known genetic loci account for only a fraction of the genetic contribution to Alzheimer&apos;s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer&apos;s disease polygenic risk score.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10700 - Other natural sciences

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

NATURE COMMUNICATIONS

ISSN

2041-1723

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

16

Strana od-do

—

Kód UT WoS článku

000713875100002

EID výsledku v databázi Scopus

—