Discovery of common and rare genetic risk variants for colorectal cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F19%3A00518235" target="_blank" >RIV/68378041:_____/19:00518235 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/19:10392338 RIV/00216208:11140/19:10392338

Výsledek na webu

<a href="https://www.nature.com/articles/s41588-018-0286-6" target="_blank" >https://www.nature.com/articles/s41588-018-0286-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-018-0286-6" target="_blank" >10.1038/s41588-018-0286-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Discovery of common and rare genetic risk variants for colorectal cancer

Popis výsledku v původním jazyce

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

Název v anglickém jazyce

Discovery of common and rare genetic risk variants for colorectal cancer

Popis výsledku anglicky

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

<a href="/cs/project/LO1503" target="_blank" >LO1503: BIOMEDIC</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

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

51

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

24

Strana od-do

76-99

Kód UT WoS článku

000454108800015

EID výsledku v databázi Scopus

2-s2.0-85058017067