A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10427930" target="_blank" >RIV/00216208:11110/21:10427930 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/21:10427930

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=bLogQMUyD3" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=bLogQMUyD3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s42003-021-01784-0" target="_blank" >10.1038/s42003-021-01784-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Popis výsledku v původním jazyce

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease. Alison Hardcastle et al. report a genome-wide meta-analysis of keratoconus, a condition affecting the cornea that causes blurred vision and often leads to blindness. They identify 36 genomic regions associated with keratoconus, 31 of which are novel, and show that the genes in these regions implicate genetic pathways involved in collagen matrix integrity and cell differentiation.

Název v anglickém jazyce

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Popis výsledku anglicky

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease. Alison Hardcastle et al. report a genome-wide meta-analysis of keratoconus, a condition affecting the cornea that causes blurred vision and often leads to blindness. They identify 36 genomic regions associated with keratoconus, 31 of which are novel, and show that the genes in these regions implicate genetic pathways involved in collagen matrix integrity and cell differentiation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30207 - Ophthalmology

Projekt

<a href="/cs/project/GA20-19278S" target="_blank" >GA20-19278S: Endotelové dystrofie rohovky - genetické příčiny a molekulární mechanismy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Communications Biology [online]

ISSN

2399-3642

e-ISSN

—

Svazek periodika

4

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

266

Kód UT WoS článku

000626074900004

EID výsledku v databázi Scopus

2-s2.0-85101817565