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Article: Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan.

Chen, Yu-Chia / Liu, Ting-Yuan / Lu, Hsing-Fang / Huang, Chung-Ming / Liao, Chi-Chou / Tsai, Fuu-Jen

2024 Volume 11, Issue 1

Abstract: Objective: To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE.: Methods: The study enrolled 2429 patients with SLE and 48 580 controls from ... ...

Abstract	Objective: To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE. Methods: The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted. Results: Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as Conclusions: The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE.
MeSH term(s)	Humans ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/epidemiology ; Taiwan/epidemiology ; Genome-Wide Association Study ; Female ; Genetic Predisposition to Disease ; Male ; Multifactorial Inheritance ; Adult ; Middle Aged ; HLA-DQ alpha-Chains/genetics ; Case-Control Studies ; Antibodies, Antinuclear/blood ; HLA-DQ beta-Chains/genetics ; Risk Factors ; Haplotypes ; Polymorphism, Single Nucleotide ; Genetic Risk Score
Chemical Substances	HLA-DQ alpha-Chains ; Antibodies, Antinuclear ; HLA-DQA1 antigen ; HLA-DQ beta-Chains ; HLA-DQB1 antigen
Language	English
Publishing date	2024-05-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2023-001035
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Article ; Online: Genetic susceptibility to prostate cancer in Taiwan: A genome-wide association study.

Bau, Da-Tian / Tsai, Chia-Wen / Chang, Wen-Shin / Yang, Jai-Sing / Liu, Ting-Yuan / Lu, Hsing-Fang / Wang, Yu-Wen / Tsai, Fuu-Jen

Molecular carcinogenesis

2024 Volume 63, Issue 4, Page(s) 617–628

Abstract: We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × ... ...

Abstract	We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × 10
MeSH term(s)	Male ; Humans ; Genome-Wide Association Study ; Genotype ; RNA, Long Noncoding/genetics ; Taiwan/epidemiology ; Genetic Predisposition to Disease ; Prostatic Neoplasms/epidemiology ; Prostatic Neoplasms/genetics ; Genetic Risk Score ; Polymorphism, Single Nucleotide ; Microfilament Proteins
Chemical Substances	RNA, Long Noncoding ; CORO2B protein, human ; Microfilament Proteins
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1004029-8
ISSN	1098-2744 ; 0899-1987
ISSN (online)	1098-2744
ISSN	0899-1987
DOI	10.1002/mc.23676
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Zs.A 2664: Show issues

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Article ; Online: Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan.

Yang, Jai-Sing / Liu, Ting-Yuan / Lu, Hsing-Fang / Tsai, Shih-Chang / Liao, Wen-Ling / Chiu, Yu-Jen / Wang, Yu-Wen / Tsai, Fuu-Jen

Molecular medicine reports

2024 Volume 30, Issue 1

Abstract: 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 ... ...

Abstract	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<5x10‑8, 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
MeSH term(s)	Humans ; Psoriasis/genetics ; Genome-Wide Association Study ; Taiwan/epidemiology ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Phenotype ; Male ; Female ; Middle Aged ; Multifactorial Inheritance ; Adult ; Risk Factors ; Haplotypes ; Genotype ; HLA Antigens/genetics ; Aged ; Genetic Risk Score
Language	English
Publishing date	2024-05-17
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2469505-1
ISSN	1791-3004 ; 1791-2997
ISSN (online)	1791-3004
ISSN	1791-2997
DOI	10.3892/mmr.2024.13239
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Article ; Online: The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases.

Lu, Hsing-Fang / Chou, Chen-Hsing / Lin, Ying-Ju / Uchiyama, Shunsuke / Terao, Chikashi / Wang, Yu-Wen / Yang, Jai-Sing / Liu, Ting-Yuan / Wong, Henry Sung-Ching / Chen, Sean Chun-Chang / Tsai, Fuu-Jen

Clinical immunology (Orlando, Fla.)

2024 Volume 260, Page(s) 109897

Abstract: Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide ... ...

Abstract	Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA103:02 - HLA-DQB103:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10
MeSH term(s)	Humans ; Genome-Wide Association Study ; Hypersensitivity/genetics ; Asthma ; Polymorphism, Single Nucleotide ; Immunoglobulin E ; Genetic Predisposition to Disease
Chemical Substances	Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2024.109897
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Zs.A 880: Show issues

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Article: Comprehensive characterization of pharmacogenes in a Taiwanese Han population.

Lu, Hsing-Fang / Liu, Ting-Yuan / Chou, Yu-Pao / Chang, Shih-Sheng / Hsieh, Yow-Wen / Chang, Jan-Gowth / Tsai, Fuu-Jen

Frontiers in genetics

2022 Volume 13, Page(s) 948616

Abstract: Pharmacogenetic (PGx) testing has not been well adopted in current clinical practice. The phenotypic distribution of clinically relevant pharmacogenes remains to be fully characterized in large population cohorts. In addition, no study has explored ... ...

Abstract	Pharmacogenetic (PGx) testing has not been well adopted in current clinical practice. The phenotypic distribution of clinically relevant pharmacogenes remains to be fully characterized in large population cohorts. In addition, no study has explored actionable PGx alleles in the East Asian population at a large scale. This study comprehensively analyzed 14 actionable pharmacogene diplotypes and phenotypes in 172,854 Taiwanese Han individuals by using their genotype data. Furthermore, we analyzed data from electronic medical records to investigate the effect of the actionable phenotypes on the individuals. The PGx phenotype frequencies were comparable between our cohort and the East Asian population. Overall, 99.9% of the individuals harbored at least one actionable PGx phenotype, and 29% of them have been prescribed a drug to which they may exhibit an atypical response. Our findings can facilitate the clinical application of PGx testing and the optimization of treatment and dosage individually.
Language	English
Publishing date	2022-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2022.948616
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Article ; Online: Functional correlations between CXCL10/IP10 gene polymorphisms and risk of Kawasaki disease.

Hsu, Yu-Wen / Lu, Hsing-Fang / Chou, Wan-Hsuan / Kuo, Ho-Chang / Chang, Wei-Chiao

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology

2020 Volume 32, Issue 2, Page(s) 363–370

Abstract: Background: Kawasaki disease (KD) is an acute systemic vasculitis syndrome with unknown pathogen. The immune system has been suggested to involve in the pathogenesis in KD. IP10 is a chemoattractant for initiating T-cell activation. The aim of this ... ...

Abstract	Background: Kawasaki disease (KD) is an acute systemic vasculitis syndrome with unknown pathogen. The immune system has been suggested to involve in the pathogenesis in KD. IP10 is a chemoattractant for initiating T-cell activation. The aim of this study was to investigate the association between genetic polymorphisms of IP10 and KD. Methods: A total of 354 KD patients and 1,709 control subjects (709 subjects in cohort 1 and 1,000 subjects in cohort 2) were enrolled in this study. Four tagging single nucleotide polymorphisms (rs3921, rs4256246, rs4508917, and rs4386624) were chosen for genotyping. Results: Our results indicated that CC genotype of rs3921 and GG genotype of rs4386624 had higher frequency in KD patients compared to control. In addition, higher plasma IP10 level was observed in CC genotype of rs3921 than CG genotype and GG genotype. C/G haplotype carriers of rs3921/rs4386624 had 5.48-fold risk for KD compared to G/C haplotype carriers. Two-locus analysis further showed the combinatorial effects of rs3921 and rs4386624 in KD susceptibility. Conclusions: This study indicated the close correlation between IP10 and the risk of Kawasaki disease.
MeSH term(s)	Case-Control Studies ; Chemokine CXCL10/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Mucocutaneous Lymph Node Syndrome/genetics ; Polymorphism, Single Nucleotide
Chemical Substances	CXCL10 protein, human ; Chemokine CXCL10
Language	English
Publishing date	2020-11-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1057059-7
ISSN	1399-3038 ; 0905-6157 ; 0906-5784
ISSN (online)	1399-3038
ISSN	0905-6157 ; 0906-5784
DOI	10.1111/pai.13381
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Zs.A 3096: Show issues

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Article: Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells.

Hour, Mann-Jen / Tsai, Fuu-Jen / Lai, I-Lu / Tsao, Je-Wei / Chiang, Jo-Hua / Chiu, Yu-Jen / Lu, Hsing-Fang / Juan, Yu-Ning / Yang, Jai-Sing / Tsai, Shih-Chang

BioMedicine

2023 Volume 13, Issue 4, Page(s) 20–31

Abstract: Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new ... ...

Abstract	Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50 and 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced autophagy vacuoles and apoptotic bodies. Combining chloroquine (CQ) and 3-methyladenine (3-MA) with HMJ-38 dramatically reduced cell viability, indicating that autophagy function as a cytoprotective mechanism. MIA-GR100 cells treated with both z-VAD-FMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspases. Epidermal growth factor receptor (EGFR) is one of HMJ-38's principal targets, as determined
Language	English
Publishing date	2023-12-01
Publishing country	China (Republic : 1949- )
Document type	Journal Article
ZDB-ID	2648006-2
ISSN	2211-8039 ; 2211-8020
ISSN (online)	2211-8039
ISSN	2211-8020
DOI	10.37796/2211-8039.1423
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Article ; Online: 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

Diabetes, obesity & metabolism

2023 Volume 25, Issue 10, Page(s) 2928–2936

Abstract: 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 ... ...

Abstract	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) DQA103:02-DQA105:01 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 DQA103:02-DQA105:01 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.
MeSH term(s)	Male ; Infant, Newborn ; Humans ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/genetics ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Risk Assessment
Language	English
Publishing date	2023-07-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.15187
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Zs.A 5442: Show issues

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Article ; Online: Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

Chiou, Jian-Shiun / Lin, Ying-Ju / Chang, Cherry Yin-Yi / Liang, Wen-Miin / Liu, Ting-Yuan / Yang, Jai-Sing / Chou, Chen-Hsing / Lu, Hsing-Fang / Chiu, Mu-Lin / Lin, Ting-Hsu / Liao, Chiu-Chu / Huang, Shao-Mei / Chou, I-Ching / Li, Te-Mao / Huang, Peng-Yan / Chien, Tzu-Shun / Chen, Hou-Ren / Tsai, Fuu-Jen

Human reproduction (Oxford, England)

2024

Abstract: Study question: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians?: Summary answer: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through ... ...

Abstract	Study question: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? Summary answer: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. What is known already: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. Study design, size, duration: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. Participants/materials, setting, methods: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. Main results and the role of chance: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. Limitations, reasons for caution: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. Wider implications of the findings: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. Study funding/competing interest(s): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. Trial registration number: N/A.
Language	English
Publishing date	2024-03-25
Publishing country	England
Document type	Journal Article
ZDB-ID	632776-x
ISSN	1460-2350 ; 0268-1161 ; 1477-741X
ISSN (online)	1460-2350
ISSN	0268-1161 ; 1477-741X
DOI	10.1093/humrep/deae060
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Article: Effect of Chinese herbal medicine therapy on risks of all-cause mortality, infections, parasites, and circulatory-related mortality in HIV/AIDS patients with neurological diseases.

Chiou, Jian-Shiun / Chou, Chen-Hsing / Ho, Mao-Wang / Tien, Ni / Liang, Wen-Miin / Chiu, Mu-Lin / Tsai, Fuu-Jen / Wu, Yang-Chang / Chou, I-Ching / Lu, Hsing-Fang / Lin, Ting-Hsu / Liao, Chiu-Chu / Huang, Shao-Mei / Li, Te-Mao / Lin, Ying-Ju

Frontiers in pharmacology

2023 Volume 14, Page(s) 1097862

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-03-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1097862
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