Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F21%3A00552826" target="_blank" >RIV/68378041:_____/21:00552826 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11140/21:10421280 RIV/00216208:11110/21:10421280 RIV/61989592:15110/21:73602827

Výsledek na webu

<a href="https://jmg.bmj.com/content/58/6/369" target="_blank" >https://jmg.bmj.com/content/58/6/369</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/jmedgenet-2020-106961" target="_blank" >10.1136/jmedgenet-2020-106961</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Popis výsledku v původním jazyce

BackgroundnMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.nObjectivenWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.nMethodsnWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.nResultsnThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54x10(-10) highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64x10(-8), highest vs lowest quintile of the weighted multifactorial score).nConclusionnWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Název v anglickém jazyce

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Popis výsledku anglicky

BackgroundnMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.nObjectivenWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.nMethodsnWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.nResultsnThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54x10(-10) highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64x10(-8), highest vs lowest quintile of the weighted multifactorial score).nConclusionnWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

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

2021

Kód důvěrnosti údajů

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

Název periodika

Journal of Medical Genetics

ISSN

0022-2593

e-ISSN

1468-6244

Svazek periodika

58

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

369-377

Kód UT WoS článku

000654442100003

EID výsledku v databázi Scopus

2-s2.0-85092010656