Genetic risk score is associated with T2DM and diabetes complications risks

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00083583" target="_blank" >RIV/00023001:_____/23:00083583 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/23:00130224 RIV/00216208:11310/23:10450073 RIV/00216208:11110/23:10450073

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378111922007417" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378111922007417</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gene.2022.146921" target="_blank" >10.1016/j.gene.2022.146921</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genetic risk score is associated with T2DM and diabetes complications risks

Popis výsledku v původním jazyce

Background: Type 2 diabetes mellitus (T2DM) is a prototypical complex disease with polygenic architecture playing an important role in determining susceptibility to develop the disease (and its complications) in subjects exposed to modifiable lifestyle factors. A current challenge is to quantify the degree of the individual&apos;s genetic risk using genetic risk scores (GRS) capturing the results of genome-wide association studies while incorporating possible ethnicity- or population-specific differences. Methods: This study included three groups of T2DM (T2DM-I, N = 1,032; T2DM-II, N = 353; and T2DM-III, N = 399) patients and 2,481 diabetes-free subjects. The status of the microvascular and macrovascular diabetes complications were known for the T2DM-I patients. Overall, 21 single nucleotide polymorphisms (SNPs) were analyzed, and selected subsets were used to determine the GRS (both weighted - wGRS and unweighted - uGRS) for T2DM risk predictions (6 SNPs) and for predicting the risks of complications (7 SNPs). Results: The strongest T2DM markers (P &lt; 0.0001) were within the genes for TCF7L2 (transcription factor 7-like 2), FTO (fat mass and obesity associated protein) and ARAP1 (ankyrin repeat and PH domain 1). The T2DM-I subjects with uGRS values greater (Odds Ratio, 95 % Confidence Interval) than six had at least twice (2.00, 1.72-2.32) the risk of T2DM development (P &lt; 0.0001), and these results were confirmed in the independent groups (T2DM-II 1.82, 1.45-2.27; T2DM-III 2.63, 2.11-3.27). The wGRS (&gt;0.6) further improved (P &lt; 0.000001) the risk estimations for all three T2DM groups. The uGRS was also a significant predictor of neuropathy (P &lt; 0.0001), nephropathy (P &lt; 0.005) and leg ischemia (P &lt; 0.0005). Conclusions: If carefully selected and specified, GRS, both weighted and unweighted, could be significant predictors of T2DM development, as well as the diabetes complications development.

Název v anglickém jazyce

Genetic risk score is associated with T2DM and diabetes complications risks

Popis výsledku anglicky

Background: Type 2 diabetes mellitus (T2DM) is a prototypical complex disease with polygenic architecture playing an important role in determining susceptibility to develop the disease (and its complications) in subjects exposed to modifiable lifestyle factors. A current challenge is to quantify the degree of the individual&apos;s genetic risk using genetic risk scores (GRS) capturing the results of genome-wide association studies while incorporating possible ethnicity- or population-specific differences. Methods: This study included three groups of T2DM (T2DM-I, N = 1,032; T2DM-II, N = 353; and T2DM-III, N = 399) patients and 2,481 diabetes-free subjects. The status of the microvascular and macrovascular diabetes complications were known for the T2DM-I patients. Overall, 21 single nucleotide polymorphisms (SNPs) were analyzed, and selected subsets were used to determine the GRS (both weighted - wGRS and unweighted - uGRS) for T2DM risk predictions (6 SNPs) and for predicting the risks of complications (7 SNPs). Results: The strongest T2DM markers (P &lt; 0.0001) were within the genes for TCF7L2 (transcription factor 7-like 2), FTO (fat mass and obesity associated protein) and ARAP1 (ankyrin repeat and PH domain 1). The T2DM-I subjects with uGRS values greater (Odds Ratio, 95 % Confidence Interval) than six had at least twice (2.00, 1.72-2.32) the risk of T2DM development (P &lt; 0.0001), and these results were confirmed in the independent groups (T2DM-II 1.82, 1.45-2.27; T2DM-III 2.63, 2.11-3.27). The wGRS (&gt;0.6) further improved (P &lt; 0.000001) the risk estimations for all three T2DM groups. The uGRS was also a significant predictor of neuropathy (P &lt; 0.0001), nephropathy (P &lt; 0.005) and leg ischemia (P &lt; 0.0005). Conclusions: If carefully selected and specified, GRS, both weighted and unweighted, could be significant predictors of T2DM development, as well as the diabetes complications development.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NV18-01-00046" target="_blank" >NV18-01-00046: Genetické skóre v predikci rizika diabetu a jeho komplikací</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Gene

ISSN

0378-1119

e-ISSN

1879-0038

Svazek periodika

849

Číslo periodika v rámci svazku

January 15

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

"art. no. 146921"

Kód UT WoS článku

000870486700009

EID výsledku v databázi Scopus

2-s2.0-85139069393