Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F20%3A00078396" target="_blank" >RIV/00209805:_____/20:00078396 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41588-020-0610-9#article-info" target="_blank" >https://www.nature.com/articles/s41588-020-0610-9#article-info</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-020-0610-9" target="_blank" >10.1038/s41588-020-0610-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease

Popis výsledku v původním jazyce

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson&apos;s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson&apos;s disease.

Název v anglickém jazyce

Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease

Popis výsledku anglicky

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson&apos;s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson&apos;s disease.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

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

—

Svazek periodika

52

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

482-493

Kód UT WoS článku

000529000400002

EID výsledku v databázi Scopus

2-s2.0-85084195663