LipidSig 2.0: integrating lipid characteristic insights into advanced lipidomics data analysis.

In the field of lipidomics, where the complexity of lipid structures and functions presents significant analytical challenges, LipidSig stands out as the first web-based platform providing integrated, comprehensive analysis for efficient data mining of lipidomic datasets. The upgraded LipidSig 2.0 (https://lipidsig.bioinfomics.org/) simplifies the process and empowers researchers to decipher the complex nature of lipids and link lipidomic data to specific characteristics and biological contexts. This tool markedly enhances the efficiency and depth of lipidomic research by autonomously identifying lipid species and assigning 29 comprehensive characteristics upon data entry. LipidSig 2.0 accommodates 24 data processing methods, streamlining diverse lipidomic datasets. The tool's expertise in automating intricate analytical processes, including data preprocessing, lipid ID annotation, differential expression, enrichment analysis, and network analysis, allows researchers to profoundly investigate lipid properties and their biological implications. Additional innovative features, such as the 'Network' function, offer a system biology perspective on lipid interactions, and the 'Multiple Group' analysis aids in examining complex experimental designs. With its comprehensive suite of features for analyzing and visualizing lipid properties, LipidSig 2.0 positions itself as an indispensable tool for advanced lipidomics research, paving the way for new insights into the role of lipids in cellular processes and disease development.

Polymorphisms of HLA genes and hypersensitivity to penicillin among patients in a Taiwanese population.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort.

OBJECTIVES: This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population. METHODS: Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE. RESULTS: In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p<0.01), higher Systemic Lupus Erythematosus Disease Activity Index scores (3.00 vs 2.37, p=0.04), elevated risks of renal involvement within the first year of SLE diagnosis, including WHO class III-IV lupus nephritis (OR 2.36, 95% CI 1.47 to 3.80, p<0.01), estimated glomerular filtration rate <60 mL/min/1.73m2 (OR 1.49, 95% CI 1.18 to 1.89, p<0.01) and urine protein-to-creatinine ratio >150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p<0.01), along with increased seropositivity risks, compared with those in the lowest quartile. Furthermore, among patients with SLE with onset before 50 years, the highest PRS quartile was significantly associated with more serious renal diseases within the first year of SLE diagnosis. CONCLUSIONS: PRS of SLE is associated with earlier onset, renal involvement within the first year of SLE diagnosis and seropositivity in Taiwanese patients. Integrating PRS with clinical decision-making may enhance lupus nephritis screening and early treatment to improve renal outcomes in patients with SLE.

Investigating the Association of Polygenic Risk Scores With Thyroid Cancer Susceptibility in a Han Chinese Population.

Background: Thyroid cancer, the leading endocrine tumor with a rising global incidence, especially in women, is influenced by both genetic and environmental factors. This study examines the relationship between polygenic risk scores (PRS) and thyroid cancer susceptibility in the Han Chinese population, as well as the impact of genetic variants on clinical outcomes. Methods: Analyzing data from 57 257 participants in the Taiwan Precision Medicine Initiative, the study employed the Affymetrix Genome-Wide TWB 2.0 SNP Array for genotyping. PRS were calculated using single nucleotide polymorphisms (SNPs) from prior genome-wide association studies, specifically PGS000087 and PGS000797, and correlated with clinical parameters like age, sex, comorbidities, and treatment methods. Results: Among 4063 participants with thyroid tumors (839 malignant, 3224 benign), higher PRS quartiles correlated significantly with increased thyroid cancer incidence. The highest quartile showed a 1.15-fold (PGS000797) and 1.14-fold (PGS000087) greater risk than the lowest quartile. Key findings included an association between higher PRS quartiles and younger onset age, along with a notable link to chronic kidney disease and thyroid hormone levels in specific SNPs. Conclusion: The study demonstrates PRS's utility in predicting thyroid cancer risk in the Han Chinese population, with higher PRS associated with increased risk and distinct clinical features. While this study focuses on the Han Chinese population, we recognize the importance of comparing PRS performance across different ancestries to fully understand ethnic genetic diversity in cancer risk assessment. Future studies should aim to include such comparative analysis.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Polygenic Risk Score in Predicting Esophageal, Oropharyngeal, and Hypopharynx Cancer Risk among Taiwanese Population.

Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies.

Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.

Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population.

BACKGROUND AND AIM: A large genetic effect of a novel gallstone-associated genetic variant, the hepatocyte nuclear factor 4α (HNF4A) rs1800961 polymorphism, has been identified through recent genome-wide association studies. However, this effect has not been validated in Asian populations. We investigated the association between the rs1800961 variant and gallstones among a Taiwanese population. METHODS: A total of 20 405 participants aged between 30 and 70 years voluntarily enrolled in the Taiwan Biobank. Self-report questionnaires, physical examinations, biochemical tests, and genotyping were used for analysis. The association of the HNF4A rs1800961 variant and other metabolic risks with gallstone disease was analyzed using multiple logistic regression models. RESULTS: The minor T allele of HNF4A rs1800961 was associated with an increased risk of gallstone, and the association remained significant even after adjustment for other risk factors including age, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and cigarette smoking (adjusted odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.31 to 2.75) in male participants. When further stratified by BMI and age, the lithogenic effect was the most significant in male participants with obesity (adjusted OR = 3.55, 95% CI = 1.92 to 6.56) and who were younger (adjusted OR = 2.45, 95% CI = 1.49 to 4.04). CONCLUSION: The novel gallstone-associated HNF4A rs1800961 variant was associated with the risk of gallstone in the Taiwanese men. Screening for the rs1800961 polymorphism may be particularly useful in assessing the risk of gallstone formation in younger or obese men.

Association between periodontitis treatment and dementia in Taiwanese adults.

BACKGROUND: The chronic systemic inflammatory response in periodontitis may be a potential risk factor for dementia, especially in adults. This study determined the association between periodontal treatment and dementia in adults and evaluated the effect of regular scaling treatment on the risk of dementia in this population. METHODS: This case-control study identified 18,930 patients with a dementia-related diagnosis from the Taiwan National Health Insurance Research Database. Scaling and periodontal emergency treatments were evaluated after 1 year and 3 years. Using multivariable logistic regression analysis to evaluate the association between periodontal emergency treatment and dementia risk. RESULTS: The results showed that scaling treatment rates were lower in the dementia cohort than the non-dementia cohort after 1 and 3 years. Patients who received periodontal emergency treatment within 3 years had a significantly increased risk of dementia. Furthermore, patients with periodontitis who did not receive scaling treatment within 3 years had a higher risk of dementia than patients without periodontitis (OR, 1.22; 95% CI, 1.10-1.35). CONCLUSION: This study demonstrated that periodontitis and dementia are associated, and that periodontitis is a risk factor for dementia in adults. The risk of dementia was dependent on the periodontal health status of adults, and our findings suggest that regular scaling can reduce the incidence of dementia in adults. Therefore, regular and routine scaling treatment is suggested for adults.

Genetic Susceptibility of HLA Alleles to Non-Steroidal Anti-Inflammatory Drug Hypersensitivity in the Taiwanese Population.

BACKGROUND: Human leukocyte antigen (HLA) genes are important in many immune processes and contribute to many adverse drug reactions. Whether genetic variations in the HLA region are associated with non-steroid anti-inflammatory drug (NSAID) hypersensitivity remains uncertain. Therefore, the aim of our study was to identify HLA genetic variations in patients with NSAID hypersensitivity in the Taiwanese population. METHODS: This hospital-based, retrospective case-control study enrolled 37,156 participants with NSAID exposure from the Taiwan Precision Medicine Initiative (TPMI), who were all genotyped and imputed to fine map HLA typing. Our study assigned 1217 cases to the NSAID allergy group and 12,170 controls to a matched group. Logistic regression analyses were utilized to explore associations between HLA alleles and NSAID hypersensitivity. RESULTS: Overall, 13,387 patients were genotyped for eight major HLA alleles. Allele frequencies were different between the two groups. In the NSAID allergy group, the genotype frequencies of HLA-A*02:01, HLA-A*34:01, and HLA-DQA1*06:01 were found to be markedly elevated compared to the control group, a significance that persisted even after applying the Bonferroni correction. Furthermore, the risk of NSAID allergy demonstrated a significant association with HLA-A*02:01 (OR = 1.29, p < 0.001) and HLA-A*34:01 (OR = 9.90, p = 0.001), in comparison to their respective counterparts. Notably, the genotype frequency of HLA-B*46:01 exhibited a significant increase in the severe allergy group when compared with the mild allergy group. CONCLUSIONS: We identified HLA genotypes linked to the onset and severity of NSAID hypersensitivity. Our findings establish a basis for precision prescription in future clinical applications.

Utilize polygenic risk score to enhance fracture risk estimation and improve the performance of FRAX in patients with osteoporosis.

This study examined the use of polygenic risk scores (PGS) in combination with the Fracture Risk Assessment Tool (FRAX) to enhance fragility fractures risk estimation in osteoporosis patients. Analyzing data from over 57,000 participants, PGS improved fracture risk estimation, especially for individuals with intermediate to low risks, allowing personalized preventive strategies. INTRODUCTION: Osteoporosis and fragility fractures are multifactorial, with contributions from both clinical and genetic determinants. However, whether using polygenic risk scores (PGS) may enhance the risk estimation of osteoporotic fracture in addition to Fracture Risk Assessment Tool (FRAX) remains unknown. This study investigated the collective association of PGS and FRAX with fragility fracture. METHODS: We conducted a cohort study from the Taiwan Precision Medicine Initiative (TPMI) at Taichung Veterans General Hospital, Taiwan. Genotyping was performed to compute PGS associated with bone mineral density (BMD). Phenome-wide association studies were executed to pinpoint phenotypes correlated with the PGS. Logistic regression analysis was conducted to ascertain factors associated with osteoporotic fractures. RESULTS: Among all 57,257 TPMI participants, 3744 (904 men and 2840 women, with a mean age of 66.7) individuals had BMD testing, with 540 (14.42%) presenting with fractures. The 3744 individuals who underwent BMD testing were categorized into four quartiles (Q1-Q4) based on PGS; 540 (14.42%) presented with fractures. Individuals with PGS-Q1 exhibited lower BMD, a higher prevalence of major fractures, and elevated FRAX-major and FRAX-hip than those with PGS-Q4. PGS was associated with major fractures after adjusting age, sex, and FRAX scores. Notably, the risk of major fractures (PGS-Q1 vs. Q4) was significantly higher in the subgroups of FRAX-major scores < 10% and 10-20%, but not in participants with a FRAX-major score ≧ 20%. CONCLUSIONS: Our study highlights the potential of PGS to augment fracture risk estimation in conjunction with FRAX, particularly in individuals with middle to low risks. Incorporating genetic testing could empower physicians to tailor personalized preventive strategies for osteoporosis.

Risk Prediction of Chronic Rhinosinusitis with or without Nasal Polyps in Taiwanese Population Using Polygenic Risk Score for Nasal Polyps.

The association between single nucleotide polymorphisms and chronic rhinosinusitis (CRS) has been determined. However, it was not known whether the polygenic risk score (PRS) for nasal polyps (NP) could predict CRS with NP (CRSwNP) or without NP (CRSsNP). The aim of this study was to investigate the association between PRSs for NP and the risk of CRS with or without NP. Data from 535 individuals with CRS and 5350 control subjects in the Taiwan Precision Medicine Initiative project were collected. Four PRSs for NP, including PGS000933, PGS000934, PGS001848, and PGS002060 from UK Biobank, were tested in these participants. They were divided into four groups according to quartiles of PRSs. The logistic regression model was performed to evaluate CRSwNP and CRSsNP risk according to PRSs for NP. The PGS002060 had the highest area under the curve at 0.534 for CRSsNP prediction and at 0.588 for CRSwNP prediction. Compared to subjects in the lowest PRS category, the PGS002060 significantly increased the odds for CRSsNP by 1.48 at the highest quintile (p = 0.003) and by 2.32 at the highest quintile for CRSwNP (p = 0.002). In addition, the odds for CRSwNP increased by 3.01 times in female CRSwNP patients (p = 0.009) at the highest quintile compared with those in the lowest PRS category. The PRSs for NP developed from European populations could be applied to the Taiwanese population to predict CRS risk, especially for female CRSwNP.

GJB2 p.V37I Mutation Associated With Moderate Nonsyndromic Hearing Loss in an Adult Taiwanese Population.

BACKGROUND: Gap junction protein beta 2 ( GJB2 ) p.V37I mutations are the most important hereditary cause of sensorineural hearing loss (SNHL) in Taiwan. Hearing outcomes are associated with hearing levels at baseline and the duration of follow-up. However, the audiological features of GJB2 p.V37I mutations in the adult population are unknown. The objectives of the present study were to investigate the audiological features, progression rate, and allele frequency of GJB2 p.V37I mutations among an adult Taiwanese population. METHODS: Subjects of this case-control study were chosen from 13,580 participants of the Taiwan Precision Medicine Initiative. The genetic variations of GJB2 p.V37I were determined by polymerase chain reaction. We analyzed existing pure-tone threshold data from 38 individuals who were homozygous or compound heterozygotes for GJB2 p.V37I, 129 who were heterozygotes, and 602 individuals who were wild-type. Phenome-wide association studies (PheWAS) analysis was also performed to identify phenotypes associated with GJB2 p.V37I. RESULTS: The minor allele frequency of GJB2 p.V37I was 0.92% in our study population. The mean hearing level of participants with a p.V37I mutation indicated moderate to severe hearing loss with 38.2% ± 22.3% binaural hearing impairment. GJB2 p.V37I was associated with an increased risk of hearing disability (odds ratio: 21.46, 95% confidence interval: 8.62 to 53.44, p < 0.001) in an autosomal recessive pattern. In addition, PheWAS discovered a significant association between GJB2 p.V37I and fracture of the humerus. GJB2 p.V37I is a pathogenic and prevalent variant of SNHL among the adult population. CONCLUSIONS: The present study recommends patients with known GJB2 p.V37I mutations receive regular audiometric evaluation and genetic counseling. Early assistive listening device intervention is suggested to improve the quality of hearing.

Sex-specific genetic variants associated with adult-onset inguinal hernia in a Taiwanese population.

Introduction: Inguinal hernia repair is one of the most common surgeries worldwide. However, there is limited information on its underlying genetic mechanism. Studies on the genetic factors related to inguinal hernia in Han Chinese are lacking. Therefore, we aimed to conduct a hospital-based study to assess the genetic factors and comorbidities underlying inguinal hernia in Taiwan. Materials and Methods: This was a retrospective case-control study. Utilizing data from the Taiwan Precision Medicine Initiative, we identified 1000 patients with inguinal hernia and 10,021 matched controls without inguinal hernia between June 2019 and June 2020. Four susceptibility loci (rs2009262, rs13091322, rs6991952, and rs3809060) associated with inguinal hernia were genotyped by the Taiwan Biobank version 2 (TWBv2) array. Inguinal hernia, surgery types, and comorbidities were obtained from the electronic health records of Taichung Veterans General Hospital. Results: Adult-onset inguinal hernia was associated with WT1 rs3809060 GT/TT genotype in males and EFEMP1 rs2009262 TC/CC genotype in females. In addition, we identified sex-specific risk factors associated with inguinal hernia; benign prostatic hyperplasia in males (OR: 3.19, 95% CI: 2.73 - 3.73, p< 0.001), chronic obstructive pulmonary disease in females (OR: 2.34, 95% CI: 1.33 - 4.11, p = 0.003) and overweight, defined by body mass index ≧24 kg/m2 (OR: 0.75, 95% CI: 0.65 - 0.86, p<0.001 in males, and OR: 0.60, 95% CI:0.37 - 0.98, p = 0.042 in females), were inversely associated with inguinal hernia. After stratifying BMI, overweight males with EFEMP1 rs2009262 TC/CC genotype exhibited a higher risk of inguinal hernia (OR: 1.31, 95% CI: 1.07 - 1.61, p = 0.01). Additionally, rs3809060 was specifically associated with male patients with direct-type inguinal hernia (OR: 1.62, 95% CI: 1.19 - 2.22, p = 0.002). Conclusion: Genetic susceptibility appears to participate in the pathogenesis of inguinal hernia in the Taiwanese population in a sex-specific manner. Future studies are needed to illuminate the complex interplay between heredity and comorbidities.

The ABCG2 rs2231142 polymorphism and the risk of nephrolithiasis: A case-control study from the Taiwan biobank.

Background: Hyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population. Methods: A total of 120,267 adults aged 30-70 years were enrolled from the Taiwan Biobank data-base in this retrospective case-control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored. Results: The frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09-1.28) and 1.12 (1.06-1.18) for TT and GT genotypes, respectively, compared with the GG genotype (p<0.001), specifically in the male population with hyperuricemia. Higher age, male sex, hyperlipidemia, hypertension, diabetes mellitus, hyperuricemia, smoking and overweight were independent risk factors for nephrolithiasis. In contrast, regular physical exercise is a protective factor against nephrolithiasis. Conclusions: ABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.

Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis.

BACKGROUND: Sepsis is a frequent complication in critically ill patients, is highly heterogeneous and is associated with high morbidity and mortality rates, especially in the elderly population. Utilizing RNA sequencing (RNA-Seq) to analyze biological pathways is widely used in clinical and molecular genetic studies, but studies in elderly patients with sepsis are still lacking. Hence, we investigated the mortality-relevant biological features and transcriptomic features in elderly patients who were admitted to the intensive care unit (ICU) for sepsis. METHODS: We enrolled 37 elderly patients with sepsis from the ICU at Taichung Veterans General Hospital. On day-1 and day-8, clinical and laboratory data, as well as blood samples, were collected for RNA-Seq analysis. We identified the dynamic transcriptome and enriched pathways of differentially expressed genes between day-8 and day-1 through DVID enrichment analysis and Gene Set Enrichment Analysis. Then, the diversity of the T cell repertoire was analyzed with MiXCR. RESULTS: Overall, 37 patients had sepsis, and responders and non-responders were grouped through principal component analysis. Significantly higher SOFA scores at day-7, longer ventilator days, ICU lengths of stay and hospital mortality were found in the non-responder group, than in the responder group. On day-8 in elderly ICU patients with sepsis, genes related to innate immunity and inflammation, such as ZDHCC19, ALOX15, FCER1A, HDC, PRSS33, and PCSK9, were upregulated. The differentially expressed genes (DEGs) were enriched in the regulation of transcription, adaptive immune response, immunoglobulin production, negative regulation of transcription, and immune response. Moreover, there was a higher diversity of T-cell receptors on day-8 in the responder group, than on day-1, indicating that they had better regulated recovery from sepsis compared with the non-response patients. CONCLUSION: Sepsis mortality and incidence were both high in elderly individuals. We identified mortality-relevant biological features and transcriptomic features with functional pathway and MiXCR analyses based on RNA-Seq data; and found that the responder group had upregulated innate immunity and increased T cell diversity; compared with the non-responder group. RNA-Seq may be able to offer additional complementary information for the accurate and early prediction of treatment outcome.

Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol-related disorder and cancer.

BACKGROUND: ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol-related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol-related disorder and cancer. METHODS: This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression. RESULTS: Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol-related disorders and was related to an increased risk of alcohol-related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR) = 1.56, p = 0.0009], cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes. CONCLUSION: rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol-related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high-risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.

Prevalence of genetically defined familial hypercholesterolemia and the impact on acute myocardial infarction in Taiwanese population: A hospital-based study.

Background: Familial hypercholesterolemia (FH) is a common genetic disorder with markedly increased risk of coronary artery diseases (CAD), especially acute myocardial infarction (AMI). However, genetic tests for FH are not always necessary in the current diagnostic criteria of FH, which might lead to underestimation of the prevalence of FH and a lack of awareness of FH-associated CAD and AMI. We aimed to explore the prevalence of genetically defined FH in the hospital-based population and to determine the impact of FH risk variants on CAD and AMI. Methods: The study participants were recruited between June 24, 2019 and May 12, 2021, at a medical center in Taiwan, in cooperation with the Taiwan Precision Medicine Initiative (TPMI) project. The prevalence of FH was calculated and the effects of FH pathogenic variants on CAD and AMI were analyzed by logistic regression models and shown as ORs and 95% CI. Results: The prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan. Highest LDL and total cholesterol levels were observed in patients with LDLR rs28942084 (LDL 219.4±55.2; total cholesterol 295.8±55.4). There was an approximately 4-fold increased risk of hyperlipidemia in subjects with the LDLR rs769446356 polymorphism (OR, 4.42; 95% CI, 1.92-10.19) and AMI in individuals with the LDLR rs730882109 polymorphism (OR, 3.79; 95% CI, 2.26-6.35), and a 2-fold increased risk of CAD in those with the LDLR rs749038326 polymorphism (OR, 2.14; 95% CI, 1.31-3.50), compared with the groups without pathogenic variants of FH. Conclusions: The prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan, which was higher than the rate observed in individuals with clinically defined FH. The risk of CAD and AMI was increased to varying degrees in subjects with different FH risk alleles. Close monitoring and risk stratification strategy are essential in high-risk patients with FH risk alleles to facilitate early detection and treatments.