J 2023

Genetic risk score is associated with T2DM and diabetes complications risks

HUBACEK, Jaroslav A., Lucie DLOUHA, Vera ADAMKOVA, Dana DLOUHA, Lukáš PÁCAL et. al.

Basic information

Original name

Genetic risk score is associated with T2DM and diabetes complications risks

Authors

HUBACEK, Jaroslav A. (203 Czech Republic, guarantor), Lucie DLOUHA (203 Czech Republic), Vera ADAMKOVA (203 Czech Republic), Dana DLOUHA (203 Czech Republic), Lukáš PÁCAL (203 Czech Republic, belonging to the institution), Kateřina KAŇKOVÁ (203 Czech Republic, belonging to the institution), David GALUŠKA (203 Czech Republic, belonging to the institution), Vera LANSKA (203 Czech Republic), Jiri VELEBA (203 Czech Republic) and Terezie PELIKANOVA (203 Czech Republic)

Edition

Gene, Amsterdam, Elsevier Science, 2023, 0378-1119

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30101 Human genetics

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.500 in 2022

RIV identification code

RIV/00216224:14110/23:00130224

Organization unit

Faculty of Medicine

UT WoS

000870486700009

Keywords in English

Diabetes; Polymorphism; Complications; Gene score

Tags

Tags

International impact, Reviewed
Změněno: 14/2/2024 13:07, Mgr. Tereza Miškechová

Abstract

V originále

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'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 < 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 < 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 (>0.6) further improved (P < 0.000001) the risk estimations for all three T2DM groups. The uGRS was also a significant predictor of neuropathy (P < 0.0001), nephropathy (P < 0.005) and leg ischemia (P < 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.

Links

MUNI/A/1370/2022, interní kód MU
Name: Patofyziologie vybraných komplexních nemocí od molekulární do systémovou úroveň
Investor: Masaryk University, Pathophysiology of selected complex diseases from molecular to systemic level
MUNI/A/1391/2021, interní kód MU
Name: Molekulární, buněčná, tkáňová a systémová patofyziologie vybraných komplexních nemocí (Acronym: KOMPLEX_PF)
Investor: Masaryk University
NV18-01-00046, research and development project
Name: Genetické skóre v predikci rizika diabetu a jeho komplikací
Investor: Ministry of Health of the CR