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

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

doi:10.1111/dom.15187

Cited by 4 publications

(4 citation statements)

References 55 publications

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“…In Taiwan, few studies have been conducted on the use of PRS for the treatment of psoriasis. Evidence suggests that diabetes mellitus is increasingly prevalent among patients with psoriasis ( 22 , 156 , 157 ). Eiris et al ( 158 ) showed a significant association between three SNPs (rs6887695, rs3212227 and rs2201841) and diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…The PRS, clinical data, or a combination of both was used to construct logistic regression models. The models were subsequently adjusted for sex, age, HLA-A*02:07 and HLA-C*06:02 ( 22 ).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the increase in sample size for GWAS has enhanced the power and effectiveness of the PRS. Therefore, a PRS based on GWAS is essential for personalized medicine ( 22 ). The PRS provides an accurate and efficient means of predicting the health status and susceptibility of an individual to disease ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

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Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Yang,

Liu,

et al. 2024

Mol Med Rep

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Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome-wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)-R software and chi-square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome-wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5×10 −8 , located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA-A*02:07 and HLA-C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta-analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

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Section: Discussionmentioning

confidence: 99%

“…The PRS, clinical data, or a combination of both was used to construct logistic regression models. The models were subsequently adjusted for sex, age, HLA-A*02:07 and HLA-C*06:02 ( 22 ).…”

Section: Methodsmentioning

confidence: 99%

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Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Yang,

Liu,

et al. 2024

Mol Med Rep

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“…Each clump comprised SNPs located within 250 kb of the index SNP and in linkage disequilibrium with the index SNP, based on pairwise threshold of r 2 = 0.1. A candidate PRS was computed using the resultant index SNPs and the corresponding estimated OR coefficients for its effect allele as weights using the "score" procedure in the GWAS of the base group [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population

Lin,

Liao,

Chen

et al. 2024

BMC Genomics

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Background Chronic Obstructive Pulmonary Disease (COPD) describes a group of progressive lung diseases causing breathing difficulties. While COPD development typically involves a complex interplay between genetic and environmental factors, genetics play a role in disease susceptibility. This study used genome-wide association studies (GWAS) and polygenic risk score (PRS) to elucidate the genetic basis for COPD in Taiwanese patients. Results GWAS was performed on a Taiwanese COPD case–control cohort with a sample size of 5,442 cases and 17,681 controls. Additionally, the PRS was calculated and assessed in our target groups. GWAS results indicate that although there were no single nucleotide polymorphisms (SNPs) of genome-wide significance, prominent COPD susceptibility loci on or nearby genes such as WWTR1, EXT1, INTU, MAP3K7CL, MAMDC2, BZW1/CLK1, LINC01197, LINC01894, and CFAP95 (C9orf135) were identified, which had not been reported in previous studies. Thirteen susceptibility loci, such as CHRNA4, AFAP1, and DTWD1, previously reported in other populations were replicated and confirmed to be associated with COPD in Taiwanese populations. The PRS was determined in the target groups using the summary statistics from our base group, yielding an effective association with COPD (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02–1.17, p = 0.011). Furthermore, replication a previous lung function trait PRS model in our target group, showed a significant association of COPD susceptibility with PRS of Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FCV) (OR 0.89, 95% CI 0.83–0.95, p = 0.001). Conclusions Novel COPD-related genes were identified in the studied Taiwanese population. The PRS model, based on COPD or lung function traits, enables disease risk estimation and enhances prediction before suffering. These results offer new perspectives on the genetics of COPD and serve as a basis for future research.

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Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions

Noble

2024

Front. Immunol.

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More than 50 years have elapsed since the association of human leukocyte antigens (HLA) with type 1 diabetes (T1D) was first reported. Since then, methods for identification of HLA have progressed from cell based to DNA based, and the number of recognized HLA variants has grown from a few to tens of thousands. Current genotyping methodology allows for exact identification of all HLA-encoding genes in an individual’s genome, with statistical analysis methods evolving to digest the enormous amount of data that can be produced at an astonishing rate. The HLA region of the genome has been repeatedly shown to be the most important genetic risk factor for T1D, and the original reported associations have been replicated, refined, and expanded. Even with the remarkable progress through 50 years and over 5,000 reports, a comprehensive understanding of all effects of HLA on T1D remains elusive. This report represents a summary of the field as it evolved and as it stands now, enumerating many past and present challenges, and suggests possible paradigm shifts for moving forward with future studies in hopes of finally understanding all the ways in which HLA influences the pathophysiology of T1D.

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

Cited by 4 publications

References 55 publications

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population

Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions

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