Combining polygenic risk scores and human leukocyte antigen variants for personalized risk assessment of type 1 diabetes in the Taiwanese population

• Published in: Diabetes, obesity & metabolism Vol. 25; no. 10; pp. 2928 - 2936
• Main Authors: Liao, Wen‐Ling, Huang, Yu‐Nan, Chang, Ya‐Wen, Liu, Ting‐Yuan, Lu, Hsing‐Fang, Tiao, Zih‐Yu, Su, Pen‐Hua, Wang, Chung‐Hsing, Tsai, Fuu‐Jen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2023; Wiley Subscription Services, Inc
• Subjects: Age; Antigens; clinical event; Diabetes; Diabetes mellitus (insulin dependent); Diagnosis; DQA1 protein; electronic medical record; Electronic medical records; Genetic analysis; Genomes; genome‐wide association studies; Histocompatibility antigen HLA; human leukocyte antigen; Ketoacidosis; Leukocytes; Medical screening; polygenic risk scores; Population studies; Risk assessment; Risk factors; type 1 diabetes; electronic medical record; type 1 diabetes; clinical event; human leukocyte antigen; genome-wide association studies; polygenic risk scores
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.15187

Aims To analyse the genome‐wide association study (GWAS) data of patients with type 1 diabetes mellitus (T1D) in order to develop a risk score for the genetic effects on T1D risk and age at diagnosis in the Taiwanese population. Materials and Methods We selected 610 patients with T1D and 2511 healthy individuals from an electronic medical record database of more than 300 000 individuals with genetic information, analysed their GWAS data, and developed a polygenic risk score (PRS). Results The PRS, based on 149 selected single‐nucleotide polymorphisms, could effectively predict T1D risk. A PRS increase was associated with increased T1D risk (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.72‐2.55). Moreover, a 1‐unit increase in standardized T1D PRS decreased the age at diagnosis by 0.74 years. Combined PRS and human leukocyte antigen (HLA) DQA1*03:02–DQA1*05:01 genotypes could accurately predict T1D risk. In multivariable models, HLA variants and PRS were independent risk factors for T1D risk (OR 3.76 [95% CI 1.54‐9.16] and 1.71 [95% CI 1.37‐2.13] for HLA DQA1*03:02–DQA1*05:01 and PRS, respectively). In a limited study population of those aged ≤18 years, PRS remained significantly associated with T1D risk. The association between T1D PRS and age at diagnosis was more obvious among males and patients aged ≤18 years. Conclusions Polygenic risk score and HLA variations enable personalized risk estimates, enhance newborn screening efficiency for ketoacidosis prevention, and addresses the gap in data on T1D prediction in isolated Asian populations.