Identifying genetically predisposed type 1 diabetes mellitus individuals in a Southern Brazilian population: The construction of a genetic risk score

Identifying genetically predisposed type 1 diabetes mellitus individuals in a Southern Brazilian population: The construction of a genetic risk score

Abstract Single nucleotide polymorphisms (SNPs) in the HLA DR/DQ region have the greatest impact on susceptibility to type 1 diabetes mellitus (T1DM). Non-HLA SNPs interact with the HLA, influencing the risk for T1DM. The aim of this study was to develop a genetic risk score (GRS) based on HLA DR/DQ...

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Main Authors: Felipe Mateus Pellenz, Mayara Souza de Oliveira, Guilherme Coutinho Kullmann Duarte, Natália Emerim Lemos, Cristine Dieter, Luís Henrique Canani, Taís Silveira Assmann, Daisy Crispim
Format: Article
Language:English
Published: Sociedade Brasileira de Genética 2025-04-01
Series:Genetics and Molecular Biology
Subjects:
Race adjusted-genetic risk score
HLA DR/DQ
single nucleotide polymorphisms
type 1 diabetes mellitus
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000200101&lng=en&tlng=en
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Summary:Abstract Single nucleotide polymorphisms (SNPs) in the HLA DR/DQ region have the greatest impact on susceptibility to type 1 diabetes mellitus (T1DM). Non-HLA SNPs interact with the HLA, influencing the risk for T1DM. The aim of this study was to develop a genetic risk score (GRS) based on HLA DR/DQ and non-HLA SNPs to discriminate patients with T1DM. The sample comprised 466 patients with T1DM and 469 controls. The rs689/INS, rs2476601/PTPN22, rs231775/CTLA-4, rs2304256/TYK2, rs2292239/ERBB3, and HLA DR/DQ SNPs were genotyped using real-time PCR. The unweighted GRS (uGRS) was calculated by summing the risk alleles of each SNP and the weighted GRS (wGRS) by multiplying the risk alleles by their odds ratios. The uGRS was higher in T1DM patients than in non-diabetic controls (0.34 ± 0.14 vs. 0.26 ± 0.13, P <0.0001), being positively correlated with HbA1c levels (P <0.0001). wGRSs exhibited higher AUCs than uGRSs. The wGRS containing only HLA DR/DQ SNPs showed an AUC of 0.75 (95% CI 0.72 - 0.78). The wGRS containing both HLA DR/DQ and non-HLA SNPs, adjusted for race, demonstrated the best discriminative power [AUC 0.91 (95% CI 0.89 - 0.93)]. The race adjusted-wGRS, including all SNPs, seems to be a useful genetic tool for assessing individual’s predisposition to T1DM.
ISSN:1678-4685

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