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Abstract Background Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA. Methods We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis. Results We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women. Conclusion According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women.

Abstract Objective To develop and validate machine learning models for predicting coronary artery disease (CAD) within a Taiwanese cohort, with an emphasis on identifying significant predictors and comparing the performance of various models. Methods This study involved a comprehensive analysis of clinical, demographic, and laboratory data from 8,495 subjects in Taiwan Biobank (TWB) after propensity score matching to address potential confounding factors. Key variables included age, gender, lipid profiles (T-CHO, HDL_C, LDL_C, TG), smoking and alcohol consumption habits, and renal and liver function markers. The performance of multiple machine learning models was evaluated. Results The cohort comprised 1,699 individuals with CAD identified through self-reported questionnaires. Significant differences were observed between CAD and non-CAD individuals regarding demographics and clinical features. Notably, the Gradient Boosting model emerged as the most accurate, achieving an AUC of 0.846 (95% confidence interval [CI] 0.819–0.873), sensitivity of 0.776 (95% CI, 0.732–0.820), and specificity of 0.759 (95% CI, 0.736–0.782), respectively. The accuracy was 0.762 (95% CI, 0.742–0.782). Age was identified as the most influential predictor of CAD risk within the studied dataset. Conclusion The Gradient Boosting machine learning model demonstrated superior performance in predicting CAD within the Taiwanese cohort, with age being a critical predictor. These findings underscore the potential of machine learning models in enhancing the prediction accuracy of CAD, thereby supporting early detection and targeted intervention strategies. Trial registration Not applicable.

Abstract Osteoporosis is a prevalent condition marked by reduced bone density and an elevated risk of fractures, especially among postmenopausal women. Exercise plays a crucial role in preventing and managing osteoporosis, with weight-bearing and impact exercises being particularly effective in enhancing bone density and mitigating disease risk. This study investigated the relationship between various types of impact exercises and osteoporosis using data from the Taiwan Biobank (TWB). The study sample comprised 5,123 individuals without osteoporosis and 1,770 individuals with the condition. Student’s t-test and logistic regression analyses were utilized to assess the associations between exercise types and osteoporosis risk. Results indicated that high-impact exercise significantly reduced the likelihood of developing osteoporosis compared to no exercise (odds ratio; OR = 0.573, 95% CI: 0.406–0.810, P = 0.002). Conversely, low-impact exercises did not show a significant overall association with osteoporosis (OR = 1.160, 95% CI: 0.932–1.445, P = 0.184). Stratified analysis by sex revealed that high-impact exercise was protective against osteoporosis in men (OR = 0.391, 95% CI: 0.202–0.755, P = 0.005), but not significantly so in women (OR = 0.671, 95% CI: 0.438–1.027, P = 0.066). These findings suggest that high-impact exercise is associated with a reduced risk of osteoporosis, particularly among Taiwanese men aged 30 to 70.

Abstract The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p

Abstract Background Metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors is influenced by environmental, lifestyle, and genetic factors. We explored whether coffee consumption and the rs301 variant of the lipoprotein lipase (LPL) gene are related to MetS. Methods We conducted multiple logistic regression analyses using data gathered from 9523 subjects in Taiwan Biobank (TWB). Results Our findings indicated that individuals who consumed coffee had a reduced odds ratio (OR) for MetS (0.750 (95% confidence interval [CI] 0.653–0.861) compared to non-coffee drinkers. Additionally, the risk of MetS was lower for individuals with the ‘TC’ and ‘CC’ genotypes of rs301 compared to those with the ‘TT’ genotype. Specifically, the OR for MetS was 0.827 (95% CI 0.721–0.949) for the ‘TC’ genotype and 0.848 (95% CI 0.610–1.177) for the ‘CC’ genotype. We observed an interaction between coffee consumption and the rs301 variant, with a p-value for the interaction of 0.0437. Compared to the reference group (‘no coffee drinking/TT’), the ORs for MetS were 0.836 (95% CI 0.706–0.992) for ‘coffee drinking/TT’, 0.557 (95% CI 0.438–0.707) for ‘coffee drinking/TC’, and 0.544 (95% CI 0.319–0.927) for ‘coffee drinking/CC’. Notably, MetS was not observed in non-coffee drinkers regardless of their rs301 genotype. Conclusion Our findings suggest that rs301 genotypes may protect against MetS in Taiwanese adults who consume coffee compared to non-coffee drinkers.

Abstract Background The kidney and eyes share common pathways and are thought to be closely connected. Chronic kidney disease and major eye diseases, such as cataract and glaucoma, are strongly associated with age. However, further investigation is needed to understand the joint impact of age and kidney diseases on eye diseases. In this study, we assessed the risk of eye diseases in relation to age and kidney failure in Taiwanese adults. Methods Our study included 127,561 cancer-free volunteers aged 30 to 70 years who participated in the Taiwan Biobank (TWB) project from 2008 to 2020. Information on the main exposures (kidney failure and age) and the outcome (eye diseases, including glaucoma, cataract, xerophthalmia, and retinal detachment) was collected through questionnaires. Results In general, kidney failure and older age were independently associated with a higher risk of eye, particularly cataract and retinal detachment: prevalence odds ratio (POR); 95% confidence interval (CI) = 2.480; 1.635–3.761 for cataract and 3.885; 1.968–7.666 for retinal detachment. A significant interaction between kidney failure and age on cataract was observed (p-value = 0.0002). Age-stratified analysis revealed a higher risk of cataract among patients with kidney failure aged below 50 (POR = 6.534; 95% CI = 2.493–17.124) and between 50 and 60 years (POR = 3.957; 95%CI = 1.986–7.881). Combining kidney failure and age (reference: no kidney failure and age 60 years. Combining cataract and age (reference: no cataract and age

IntroductionAlcohol consumption can induce a neuroinflammatory response and contribute to the progression of neurodegeneration. However, its association with Parkinson’s disease (PD), the second most common neurodegenerative disorder, remains undetermined. Recent studies suggest that the glycoprotein non-metastatic melanoma protein B (GPNMB) is a potential biomarker for PD. We evaluated the association of rs199347, a variant of the GPNMB gene, with alcohol consumption and methylation upstream of GPNMB.MethodsWe retrieved genetic and DNA methylation data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2016. After excluding individuals with incomplete or missing information about potential PD risk factors, we included 1,357 participants in our final analyses. We used multiple linear regression to assess the association of GPNMB rs199347 and chronic alcohol consumption (and other potential risk factors) with GPNMB cg17274742 methylation.ResultsThere was no difference between the distribution of GPNMB rs199347 genotypes between chronic alcohol consumers and the other study participants. A significant interaction was observed between the GPNMB rs199347 variant and alcohol consumption (p = 0.0102) concerning cg17274742 methylation. Compared to non-chronic alcohol consumers with the AA genotype, alcohol drinkers with the rs199347 GG genotype had significantly lower levels (hypomethylation) of cg17274742 (p = 0.0187).ConclusionAlcohol consumption among individuals with the rs199347 GG genotype was associated with lower levels of cg17274742 methylation, which could increase expression of the GPNMB gene, an important neuroinflammatory-related risk gene for PD.

Abstract Recent studies showed significant associations between socio-demographic, lifestyle factors, polymorphic variant rs6265, and smoking cessation behaviours. We examined rs6265 TT, TC and CC genotypes and their association with socio-demographic and other variables, including mental health status, drinking, exercise, and smoking behaviour among Taiwanese adults. Data on rs6265 were retrieved from the Taiwan Biobank, which contained genetic data collected between 2008 to 2019 from 20,584 participants (aged 30–70 years). Participants who smoked for more than 6 months prior to enrolment were categorized as smokers. If they had smoked and later quit for more than 6 months, they were classified as former smokers. Information regarding drinking, exercise, depression, and bipolar disorder were obtained through questionnaires and were categorized as either as affirmative (yes) or negative (no) responses. In contrast to previous studies, we found that the association between the polymorphism rs6265 and smoking behaviour was not significant (P-value = 0.8753). Males with lower education levels, young persons, and alcohol drinkers showed significant smoking behaviours (P-value

Background:Over the past few decades, gout and diseases like metabolic syndrome (MetS) have become more prevalent. Attempts have been made in Taiwan to identify the genes responsible for gout. A few gene loci, among them SLC2A9, have been identified using Taiwan Biobank (TWB) data. We, therefore, examined whether MetS could also account for the association between polymorphism SLC2A9 rs3733591 and gout.Methods:The final analysis consisted of 73,558 subjects, of whom 2,709 had gout. To estimate the likelihood of gout occurrence based on rs3733591 and MetS, we used logistic regression models.Results:Rs3733591-TC + CC compared to TT genotype was associated with gout (OR, 1.15; 95% CI, 1.06–1.25). Also associated with gout was MetS (OR, 1.21; 95% CI, 1.10–1.33). A significant interaction was seen between rs3733591 and MetS (p-value = 0.039). Using rs3733591-TT/no MetS as the reference group, the ORs (95% CI) for gout was 1.24 (1.11–1.38) for TC + CC/no MetS, 1.35 (1.17–1.56) for TT/MetS, and 1.39 (1.22–1.58) for TC + CC/MetS. However, subgroup analysis defined by sex showed no significant associations in women.Conclusion:In summary, metabolic syndrome and SLC2A9 rs3733591 genotypes were interactively associated with gout in Taiwanese men, but not women.

BackgroundCigarette smoking and particulate matter (PM) with aerodynamic diameter Q3, corresponding to PM2.5 ≤ 27.137, 27.137 38.205 μg/m3.ResultsThe prevalence of MS was significantly different according to PM2.5 exposure (p-value = 0.0280) and cigarette smoking (p-value 38.205 μg/m3, respectively. The risk of MS was significantly higher among former and current smokers with OR; 95% CI = 1.062; 1.008–1.118 and 1.531; 1.450–1.616, respectively, and a dose-dependent p-value 38.205 μg/m3, respectively. According to PM2.5 quartiles, current smokers had a higher risk of MS, regardless of PM2.5 levels (OR); 95% CI = 1.605; 1.444–1.785, 1.561; 1.409–1.728, 1.359; 1.211–1.524, and 1.585; 1.418–1.772 for PM2.5 ≤ 27.137, 27.137 38.205 μg/m3, respectively. After combining both exposures, the group, current smokers; PM2.5 > 38.205 μg/m3 had the highest odds (1.801; 95% CI =1.625–1.995).ConclusionPM2.5 and cigarette smoking were independently and jointly associated with a higher risk of MS. Stratified analyses revealed that cigarette smoking might have a much higher effect on MS than PM2.5. Nonetheless, exposure to both PM2.5 and cigarette smoking could compound the risk of MS.

Abstract Background Uterine fibroids (UFs) are uterine smooth muscle neoplasms that affect women, especially during the reproductive stage. Both genetic and lifestyle factors affect the onset of the disease. We examined the association between the estrogen receptor 1 (ESR1) rs2234693 variant (whose genotypes are TT, TC, and CC) and UFs in Taiwanese premenopausal and postmenopausal women. Methods We linked individual-level data of 3588 participants from the Taiwan Biobank to the National Health Insurance Research Database at the Health and Welfare Data Science Center. The association of the ESR1 rs2234693 variant and other variables with UFs was determined by multiple logistic regression, and the results were presented as odds ratios and 95% confidence intervals (CIs). Results The 3588 participants comprised 622 cases and 2966 controls. In all the participants, the ESR1 rs2234693 TC and CC genotypes compared to the reference genotype (TT) were associated with a lower risk of UFs. However, the results were significant only for the CC genotype (OR; 95% CI = 0.70; 0.52–0.93). Noteworthy, the association of TC and CC with UFs was dose-dependent (p-trend = 0.012). Based on menopausal status, both TC and CC were significantly and dose-dependently associated with a lower risk of UFs in premenopausal women (OR; 95% CI = 0.76; 0.59–0.98 for TC and 0.64; 0.43–0.95 for CC: p-trend = 0.010). Conclusion The TC and CC genotypes of the ESR1 rs2234693 variant may reduce susceptibility to UFs, especially in premenopausal women.

BackgroundThe aetio-pathologenesis of hypertension is multifactorial, encompassing genetic, epigenetic, and environmental factors. The combined effect of genetic and epigenetic changes on hypertension is not known. We evaluated the independent and interactive association of MTHFR rs1801133 single nucleotide polymorphism (SNP) and MTHFR promoter methylation with hypertension among Taiwanese adults.MethodsWe retrieved data including, MTHFR promoter methylation, MTHFR rs1801133 genotypes (CC, CT, and TT), basic demography, personal lifestyle habits, and disease history of 1,238 individuals from the Taiwan Biobank (TWB).ResultsThe distributions of hypertension and MTHFR promoter methylation quartiles (β

BackgroundParkinson’s disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals.MethodsWe analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension.ResultsOur results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (β = −0.00242; p = 0.0026), but not in females (β = −0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (β = −0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078).ConclusionThis study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies.

Background Although previous studies have shown that aerobic and resistance exercise increase high-density lipoprotein cholesterol (HDL-C) levels, the optimal type of exercise has not been determined. Therefore, the purpose of this study was to investigate the association of jogging (a type of aerobic exercise) and weight training (a type of resistance exercise) with HDL-C levels in Taiwanese adults. Methods The data used in this cross-sectional study were obtained from the Taiwan Biobank (TWB), which is a national health resource that contains the genetic information of Taiwanese volunteers aged 30–70 years. A total of 75,635 subjects (47,881 women and 27,754 men) were included in this study. The subjects were divided into four groups: jogging (n = 2,278), weight training (n = 522), mixed exercise (n = 519), and no exercise (n = 72,316). The TWB data were collected through questionnaires (e.g. basic characteristics, lifestyle factors, and disease history), biochemical tests, and anthropometric measurements. Results Compared with no exercise, jogging, weight training, and mixed exercise were all associated with higher HDL-C levels (β = 2.5470, 2.6249, and 3.2117, respectively). As seen, the β value was highest for the mixed exercise group, followed by weight training and then jogging (p for trend

Abstract Background: Epidemiological studies have identified common risk factors for cerebral stroke worldwide. Some of these factors include hypertension, diabetes, smoking, excessive drinking, and dyslipidemia. It is important to note, however, that genetic factors can also contribute to the occurrence of stroke. Here, we evaluated the association of ischemic stroke with rs12514417 polymorphism of the alcohol metabolizing gene, aldehyde dehydrogenase 7A1 (ALDH7A1) and alcohol consumption. Methods: Taiwan Biobank (TWB) data collected between 2008 and 2015 were available for 17,985 subjects. The odd ratios for stroke were obtained using logistic regression models. Results: Among eligible subjects (n = 17,829), 897 had ischemic stroke and 70 had hemorrhagic stroke. Subjects with ischemic stroke were older (mean ± SE, 58.45 ± 8.19 years vs. 48.33 ± 10.89 years, p

In various cross-sectional and longitudinal studies, exercise has been associated with cardiometabolic outcomes, including high-density lipoprotein (HDL) cholesterol. Exercise-induced changes in HDL cholesterol seem to be affected by genetic polymorphisms. In this study, we examined whether variant APOE rs7412 is involved in the association between HDL cholesterol and exercise. From adults assessed in Taiwan Biobank (TWB) between 2008 and 2019, we analyzed data from 57,638 normolipidemic subjects. To examine the association between exercise, APOE rs7412, and HDL cholesterol, a multiple linear regression model was used. A higher HDL was associated with both aerobic exercise (regression coefficient [mg/dL] beta- (β), 1.112; 95% confidence interval (CI); 0.903–1.322) and resistance exercise (β, 2.530; 95% CI, 2.093–2.966). In comparison with the APOE rs7412-CC genotype, the β was 2.589 (95% CI, 2.329–2.848) among those with the CT + TT genotype. Compared to adults who had the CC genotype and did not exercise (the CC/no exercise group), the β-coefficient determined for the different genotype and exercise groups was 1.135 (95% CI, 0.911–1.359) for the CC genotype and aerobic exercise group, 2.753 (95% CI, 2.283–3.322) for the CC genotype and resistance exercise group, 2.705 (95% CI, 2.390–3.020) for the CT + TT genotype and no exercise group, 3.682 (95% CI, 3.218–4.146) for the CT + TT genotype and aerobic exercise group, and 3.855 (95% CI, 2.727–4.982) for the CT + TT genotype and resistance exercise group, respectively. This study demonstrates that self-reported aerobic and resistance exercise both raised HDL levels, yet resistance exercise was associated with a greater increase, particularly among Taiwanese subjects carrying the APOE rs7412-CT+TT genotype.

BackgroundVaricose veins (VVs), a common vascular disease is associated with a huge medical burden. The prevalence in women surpasses that in men. The role of vegetarian diets in the pathogenesis of the disease remains inconclusive. In this study, we examined the risk of VVs in vegetarian and non-vegetarian men and women.MethodsThe study involved 9905 adults whose data were obtained from Taiwan Biobank between 2008 and 2020. Information on VVs, sex, and vegetarian diets was obtained from participants’ self-responses to the Taiwan Biobank questionnaires.ResultsThe study subjects consisted of 4,142 men and 5,763 women. About 12% of men and 35% of women had VVs. Study participants were predominantly non-vegetarians (91.84% were men and 88.24% were women). Women had a higher risk of VVs than men. The odds ratio (OR); 95% confidence interval (CI) was 3.414; 2.995–3.891. There was a significant interaction between sex and vegetarian diets (p = 0.0034). Women were at higher risk of VVs than men both in the vegetarian (OR = 1.877, 95% CI = 1.270–2.774) and non-vegetarian (OR = 3.674, 95% CI = 3.197–4.223) groups. Based on vegetarian diets, only vegetarian men had a higher risk of VVs (OR = 1.453, 95% CI = 1.069 to 1.976). Based on the sex-stratified model, the risk of VVs was significantly higher in vegetarian men (OR = 1.457, 95% CI = 1.072–1.979), and in vegetarian and non-vegetarian women with corresponding ORs (95% CI) of 3.101 (2.528–3.803) and 3.599 (3.140–4.124), respectively.ConclusionWomen were more susceptible to varicose veins compared to men, regardless of diet. However, in terms of diet, only men who followed a vegetarian diet were at greater risk for developing VVs.

Abstract Background Bet1 Golgi vesicular membrane trafficking protein-like (BET1L) rs2280543 single nucleotide polymorphism (SNP) and diet have been independently associated with uterine leiomyoma (UL). However, whether the SNP and diet could jointly influence the risk of UL is yet to be assessed. Therefore, we investigated the independent and interactive effects of vegetarian diet and BET1L rs2280543 on uterine fibroids in Taiwanese women. Methods We linked participants’ electronic data in the Taiwan Biobank (TWB) database to their medical records in the National Health Insurance Research Database (NHIRD). The TWB had genotypic, lifestyle, and biochemical data between 2008 and 2015 and the NHIRD had data on disease diagnoses between 1998 and 2015. In this study, we included 1997 premenopausal women with complete data. Results Compared to participants with the BET1L rs2280543 CC genotype (wildtype), those with CT/CC genotype had an odds ratio (OR) of 0.69 and a 95% confidence interval (CI) of 0.51–0.93. Vegetarian diet and UL were not significantly associated: OR = 1.09 and 95% CI = 0.77–1.55. However, the test for interaction between rs2280543 and vegetarian diet was significant (p = 0.046). Compared to individuals with the CC genotype, the risk of UL was lower among vegetarians with the CT/TT genotype: OR (95% CI) = 0.15 (0.05–0.47). Conclusion The BET1L rs2280543 CT/TT genotype was associated with a lower risk of UL especially among vegetarians.

Abstract Background Type 2 diabetes mellitus (T2DM) is caused by a combination of environmental, genetic, and epigenetic factors including, fasting blood glucose (FBG), genetic variant rs841853, and cg19693031 methylation. We evaluated the interaction between rs841853 and cg19693031 on the FBG levels of non-diabetic Taiwanese adults. Methods We used Taiwan Biobank (TWB) data collected between 2008 and 2016. The TWB data source contains information on basic demographics, personal lifestyles, medical history, methylation, and genotype. The study participants included 1300 people with DNA methylation data. The association of cg19693031 methylation (stratified into quartiles) with rs841853 and FBG was determined using multiple linear regression analysis. The beta-coefficients (β) and p-values were estimated. Results The mean ± standard deviation (SD) of FBG in rs841853-CC individuals (92.07 ± 7.78) did not differ significantly from that in the CA + AA individuals (91.62 ± 7.14). However, the cg19693031 methylation levels were significantly different in the two groups (0.7716 ± 0.05 in CC individuals and 0.7631 ± 0.05 in CA + AA individuals (p = 0.002). The cg19693031 methylation levels according to quartiles were β

Abstract Background Gallstones are abnormal masses caused by impaired metabolism of cholesterol, bilirubin, or bile salts in the gallbladder or biliary tract. ATP-binding cassette subfamily G member 8 (ABCG8) is a protein that regulates cholesterol efflux from the liver. Genome-wide association studies (GWAS) and meta-analyses of GWAS revealed the ABCG8 rs11887534 variant as the most common genetic determinant of gallstones in humans. These findings have not been extensively replicated in Taiwanese. Therefore, we appraised the relationship between gallstones and rs11887534 in a relatively large Taiwanese sample. Methods We retrieved data collected through questionnaires, physical and biochemical tests from the Taiwan Biobank Bank (TWB). The study participants comprised 7388 men and 13,880 women who voluntarily enrolled in the Taiwan Biobank project between 2008 and 2019. Gallstones were self-reported. Results The overall sample size was 21,268 comprising 938 gallstone patients and 20,330 non-gallstone individuals. Among the participants, 20,640 had the GG and 628 had the GC + CC genotype. At p-value

Abstract Background In July 1984, Taiwan officially began a nationwide hepatitis B virus (HBV) vaccination program where only infants born to HBsAg-positive mothers were vaccinated free of charge until June 1986. However, from July 1986, all infants were vaccinated against HBV. The impact of the July 1986 HBV vaccination program on first-time blood donors has not been exhaustively studied. We, therefore, determined the risk of HBV among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. Methods Initially, we recruited 857,310 first-time blood donors whose data were collected between 2013 and 2018 from 5 blood donation centers in Taiwan. However, we excluded donors with incomplete and outlying data (n = 12,213) and those born between July 1984 and June 1986 (n = 21,054). The final study participants comprised 9118 HBV positive and 814,925 HBV negative individuals. We divided the participants into two birth cohorts (born before and after July 1986) and assumed that those born before July 1986 were not vaccinated at birth while those born after July 1986 were vaccinated. Results The prevalence of HBV among those born before and after July 1986 was 4.53 and 0.25%, respectively. Individuals born after July 1986 had a lower risk of HBV than those born before July 1986. The adjusted odds ratio (OR), 95% confidence interval (CI) was 0.16, 0.13–0.19. Men had a higher risk of HBV than women (OR = 1.40, 95% CI = 1.34–1.47). The interaction between sex and birth date was significant (p-value = 0.0067). Stratification of participants by birth date revealed a higher risk of HBV in men compared to women in both birth cohorts. The OR, 95% CI was 1.47, 1.40–1.55 for those born before July 1986 but declined to 1.15, 1.02–1.29 for those born after July 1986. Conclusions The risk of HBV was lower among those born after than those born before the July 1986 vaccination program. In both cohorts, the risk was high in men relative to women. The seemingly protective effect among those born after July 1986 was higher in women than men.

Abstract Background Hypertension increases the likelihood of cardiovascular diseases (CVDs). Cytochrome P450 1A2 (CYP1A2) single nucleotide polymorphism (SNP) is related to caffeine metabolism and the risk of CVD among coffee drinkers. CYP1A2 rs762551 influenced the risk of stroke among hypertensive patients. We examined the relationship between hypertension and coffee drinking based on CYP1A2 rs762551 SNP in Taiwanese adults. Methods We used data contained in the Taiwan Biobank database (2011–2018) and included 19,133 participants having complete information on hypertension, rs762551 polymorphism, coffee intake, etc. The risk of hypertension was determined using multiple logistic regression. Results Coffee intake was significantly associated with a lower risk of hypertension. The odds ratio (OR), 95% confidence interval (CI), and p-value were 0.877, 0.807–0.954, and 0.0032, respectively. CYP1A2 rs762551 was not significantly associated with the risk of hypertension, but it had a significant interactive association with coffee drinking (p value = 0.0303). After stratification by rs762551 genotypes, the inverse coffee drinking-hypertension association was retained, but significant results were observed only in those with the AC + CC genotype (OR 0.678, 95% CI 0.722–900, p value = 0.0001). According to the combination of coffee drinking and rs762551 genotypes (reference group: no coffee drinking and rs762551 AA), the coffee drinking-AC + CC group had a lower risk of hypertension (OR 0.888, 95% CI 0.789–0.999, p value = 0.0483). Conclusion Coffee drinking, particularly among individuals with the CYP1A2 rs762551 AC + CC genotype was associated with lower odds of hypertension.

Abstract Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p

Background/AimRecent studies reported that folate supplementation has beneficial effects on major depression. The Methylenetetrahydrofolate reductase (MTHFR) enzyme is crucial in folate metabolism. This population-based study examined the association between MTHFR rs17367504 polymorphism and major depressive disorder based on exercise habits.MethodsTaiwan Biobank (TWB) provided demographic and genotype data between 2008 and 2015. The biobank participants were Taiwanese aged 30 to 70. Data on major depressive disorder (MDD) were obtained from the National Health Insurance Research Database (NHIRD).ResultsA total of 636 individuals were identified with MDD, whereas 17,298 individuals were considered controls. The associations of MTHFR rs17367504 and exercise with MDD risk were estimated using logistic regression models. The distribution of MTHFR rs17367504 genotype frequencies differed significantly between the MDD and control groups. We found that, compared with the AA genotype, the GG genotype was associated with a significantly increased risk of MDD [adjusted odds ratio (aOR), 1.76; 95% confidence interval (CI), 1.05–2.94; p = 0.033]. We found an interaction (p = 0.04) between rs17367504 and exercise, a well-known protective factor for MDD. A substantial increase in the risk of MDD was found among those with GG genotypes who did not exercise (aOR, 2.93; 95% CI, 1.66–5.17; p < 0.001).ConclusionsOur findings indicate that MDD is related to MTHFR rs17367504 and exercise, though the mechanisms remain to be determined.

Abstract Background Gout stems from both modifiable and genetic sources. We evaluated the risk of gout among Taiwanese adults with aldehyde dehydrogenase-2 (ALDH2) rs671 single nucleotide polymorphism (SNP) according to body mass index (BMI) and alcohol drinking. Methods We obtained information of 9253 individuals having no personal history of cancer from the Taiwan Biobank (2008–2016) and estimated the association between gout and independent variables (e.g., rs671, BMI, and alcohol drinking) using multiple logistic regression. Results Alcohol drinking and abnormal BMI were associated with a higher risk of gout whereas the rs671 GA+AA genotype was associated with a lower risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were 1.297 and 1.098–1.532 for alcohol drinking, 1.550 and 1.368–1.755 for abnormal BMI, and 0.887 and 0.800–0.984 for GA+AA. The interaction between BMI and alcohol on gout was significant for GG (p-value = 0.0102) and GA+AA (p-value = 0.0175). When we stratified genotypes by BMI, alcohol drinking was significantly associated with gout only among individuals with a normal BMI (OR; 95% CI = 1.533; 1.036–2.269 for GG and 2.109; 1.202–3.699 for GA+AA). Concerning the combination of BMI and alcohol drinking among participants stratified by genotypes (reference, GG genotype, normal BMI, and no alcohol drinking), the risk of gout was significantly higher in the following categories: GG, normal BMI, and alcohol drinking (OR, 95% CI = 1.929, 1.385–2.688); GG, abnormal BMI, and no alcohol drinking (OR, 95% CI, = 1.721, 1.442–2.052); GG, abnormal BMI, and alcohol drinking (OR, 95% CI = 1.941, 1.501–2.511); GA+AA, normal BMI, and alcohol drinking (OR, 95% CI = 1.971, 1.167–3.327); GA+AA, abnormal BMI, and no alcohol drinking (OR, 95% CI = 1.498, 1.256–1.586); and GA+AA, abnormal BMI, and alcohol drinking (OR, 95% CI = 1.545, 1.088–2.194). Conclusions Alcohol and abnormal BMI were associated with a higher risk of gout, whereas the rs671 GA+AA genotype was associated with a lower risk. Noteworthy, BMI and alcohol had a significant interaction on gout risk. Stratified analyses revealed that alcohol drinking especially among normal-weight individuals might elevate the risk of gout irrespective of the genotype.

Abstract Background DNA methylation of Cadherin 13 (CDH13), a tumor suppressor gene is associated with gene repression and carcinogenesis. We determined the relation of dietary fat and sex with CDH13 cg02263260 methylation in Taiwanese adults. Methods Data of 870 eligible participants (430 men and 440 women) between 30 and 70 years were obtained from the Taiwan Biobank (TWB) database. The association of dietary fat and sex with CDH13 cg02263260 methylation was determined using multiple linear regression. Results The association between sex and cg02263260 methylation was significant: beta-coefficient (β) = 0.00532; 95% confidence interval (CI) = 0.00195–0.00868. Moreover, the interaction between sex and dietary fat on cg02263260 methylation was significant (P-value = 0.0145). After stratification by sex, the association of dietary fat with cg02263260 methylation was significant only in women. Specifically, high dietary fat was positively associated with cg02263260 methylation in women (β = 0.00597; 95% CI = 0.00061–0.01133) and the test for trend was significant (P-value = 0.0283). Conclusion High fat intake was significantly associated with higher cg02263260 methylation in women and the test for trend was significant. These findings suggest that the association of fat intake and CDH13 cg02263260 might vary by sex and CDH13 cg02263260 methylation levels in women might increase as fat intake increases.

Abstract Background Particulate matter (PM) < 2.5 μm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5 and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise. Methods We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5 data from the Air Quality Monitoring Database (AQMD) and estimated participants’ exposure using residential addresses. Results DLEC1 methylation and PM2.5 were positively associated: beta coefficient (β) = 0.114 × 10−3; p value = 0.046. The test for interaction between exercise and PM2.5 on DLEC1 methylation was significant (p value = 0.036). After stratification by exercise habits, PM2.5 and DLEC1 methylation remained significantly associated only among those who exercised regularly (β = 0.237 × 10−3; p value = 0.007). PM2.5 quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5 < 27.37 μg/m3 (β = − 5.280 × 10−3; p value = 0.009). After combining exercise habits and PM2.5 quartiles, one stratum (i.e., regular exercise and PM2.5 < 27.37 μg/m3) was inversely associated with DLEC1 methylation (β = -5.160 × 10−3, p value = 0.007). Conclusions We found significant positive associations between PM2.5 and DLEC1 promoter methylation. Regular exercise at PM2.5 < 27.37 μg/m3 seemingly regulated DLEC1 promoter methylation.

Type 2 diabetes (T2D) and liver cirrhosis remain significant public health threats in Taiwan. These conditions are reported to be associated with the rs738409 polymorphism of the patatin-like phospholipase domain-containing protein three gene (PNPLA3) in European populations. We assessed the effect of T2D and PNPLA3 rs738409 polymorphism on liver cirrhosis among Taiwan Biobank (TWB) participants. In total, 17,985 participants in TWB had their health records linked to the National Health Insurance Research Database (NHIRD). Participants included those who visited the assessment centers between 2008 and 2015, with an age range between 30 and 70 years of age. We performed logistic regression analysis to investigate the odds ratios (OR) for liver cirrhosis among participants based on the T2D status and rs738409 genotypes. Genotyping was performed using the Axiom Genome-Wide TWB Array Plate. In our analysis, 150 of the 17,619 eligible participants were identified as cirrhosis cases. Based on the univariate analysis, liver cirrhosis was positively associated with T2D (OR, 1.83; 95% CI 1.23–2.70) whereas, the variant rs738409 was not (regardless of the genetic model). The variant and T2D, however, showed significant interactions in the additive, genotype, and dominant models (p values of 0.0302, 0.0395, and 0.0455, respectively). We observed a statistically significant association between T2D and liver cirrhosis and variant rs738409 with an OR of 1.71 (95% CI, 1.03–2.84) for individuals carrying a G allele compared to those with a C allele and 2.92 (95% CI 1.07–7.99) for GG compared to CC individuals. According to our study, Taiwanese adults with T2D and the rs738409 GG genotype are more likely to develop liver cirrhosis.

BackgroundGlycosylated hemoglobin (HbA1c) reflects the average blood sugar over the past eight to twelve weeks. Several demographic and lifestyle factors are known to affect HbA1c levels. We evaluated the association of HbA1c with aerobic and resistance exercise in non-diabetic Taiwanese adults based on the waist-hip ratio (WHR).MethodsWe conducted this study based on TWB data collected from 90,958 individuals between 2008 and 2019. We estimated the Beta (β) coefficient and 95% confidence intervals (CI) for HbA1c using multivariate regression models.ResultsBased on the multivariate analysis, lower HbA1c levels were associated with both resistance exercise (β-coefficient = -0.027, 95% CI -0.037 to -0.017) and aerobic exercise (β-coefficient = 0.018, 95% CI, -0.023 to -0.013). Higher HbA1c levels were associated with abnormal WHR compared to normal WHR (β-coefficient = 0.091, 95% CI, 0.086 to 0.096). We detected an interaction between exercise and WHR (p for interaction = 0.0181). To determine the magnitude of the interaction, we performed additional analyses (with the reference group being 'abnormal WHR with no exercise') and observed substantial decreases in HbA1c regardless of the WHR and exercise category. However, the largest reduction occurred in the 'normal WHR and resistance exercise' group (β = -0.121, 95% CI, -0.132 to -0.109).ConclusionsWe found that normal resistance exercise, coupled with a normal WHR was significantly associated with lower HbA1c levels among non-diabetic individuals in Taiwan.

Abstract Background Air pollution is a global public health concern. The World Health Organization has recently set up a goal of saving 7 million people globally by 2030 from air pollution related death. We conducted an ecological study of geographical variation to explore the association between air pollution (specifically, particulate matter

Abstract Background Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter

Abstract Background Results from studies investigating the association between coffee consumption and osteoporosis or bone mineral density (BMD) have been inconsistent. This longitudinal study was performed to assess the effect of coffee drinking on bone health of Taiwanese adults. Methods Data were retrieved from the Li-Shin (Landseed) Hospital in Taoyuan City. In 2006, 6152 participants completed a questionnaire on coffee drinking and other lifestyle factors. In 2014, 5077 of them were followed up. Nonetheless, a total of 2395 participants with incomplete data were excluded. The final analyses included 2682 participants comprising 1195 men and 1487 women (706 premenopausal and 781 postmenopausal). T-scores were derived from the osteo-sono assessment index (OSI) which is a surrogate of BMD. Coffee drinking was categorized as “no, medium, and high” based on the number of cups that were consumed per week in both 2006 and 2014. Results In general, medium and high coffee drinking were associated with higher T-scores. However, significant results were observed only among high drinkers (β = 0.158; P = 0.0038). Nonetheless, the test for linear trend was significant (P = 0.0046). After stratification by sex, medium and high coffee drinking were associated with higher T-scores. However, significant results were prominent only among high male drinkers (β = 0.237; P = 0.0067) and the test for trend was significant (P = 0.0161). Based on menopausal status, coffee drinking was associated with higher T-scores. Nevertheless, significant results were found only among premenopausal women (β = 0.233; P = 0.0355 and β = 0.234; P = 0.0152 for medium and high coffee drinking, respectively. The test for linear trend was significant (P = 0.0108). Conclusion Coffee drinking was significantly associated with higher T-scores hence, a lower risk of osteoporosis in men and premenopausal women.

We examined the association between high-density lipoprotein cholesterol (HDL-C), and exercise and vegetarian diets, in Taiwanese adults, based on the Methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism. Using regression models, we analyzed historical data collected from 9255 Taiwan Biobank (TWB) participants from 2008 through 2015. Exposure to exercise was associated with higher HDL-C (β = 1.0508 and 1.4011 for GG and GA + AA individuals, respectively), whereas a vegetarian diet was associated with lower HDL-C (β = −6.2793 and −4.6359 for those with GG and GA + AA genotype, respectively). We found an interaction between exercise and diet among GG individuals (p = 0.0101). Compared with no exercise/no vegetarian diet, vegetarian diet/no exercise was associated with a 5.1514 mg/dl reduction in HDL-C among those with GG genotype (β = −5.1514, p < 0.0001) and a 4.8426 mg/dl reduction (β = −4.8426, p < 0.0001) among those with GA + AA genotype. Vegetarian diets in combination with exercise predicted a 6.5552 mg/dl reduction in HDL-C among GG individuals (β = −6.5552) and a 2.8668 mg/dl reduction among GA + AA individuals (p < 0.05). These findings demonstrated that vegetarian diet alone was associated with lower HDL-C, no matter the rs1801133 genotype. However, the inclusion of regular exercise predicted much lower levels among GG individuals, whereas levels among GA + AA individuals were relatively higher.

A complex interplay of several genetic and lifestyle factors influence coronary heart disease (CHD). We determined the interaction between coffee consumption and the tribbles pseudokinase 1 (TRIB1) rs17321515 variant on coronary heart disease (CHD). Data on CHD were obtained from the National Health Insurance Research Database (NHIRD) while genotype data were collected from the Taiwan Biobank (TWB) Database. From the linked electronic health record data, 1116 individuals were identified with CHD while 7853 were control individuals. Coffee consumption was associated with a lower risk of CHD. The multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) was 0.84 (0.72–0.99). Association of CHD with the TRIB1 rs17321515 variant was not significant. The OR (95% CI) was 1.01 (0.72–0.99). There was an interaction between TRIB1 rs17321515 and coffee consumption on CHD risk (p for interaction = 0.0330). After stratification by rs17321515 genotypes, coffee drinking remained significantly associated with a lower risk of CHD only among participants with GG genotype (OR, 0.62; 95% CI, 0.45–0.85). In conclusion, consumption of coffee was significantly associated with a decreased risk of CHD among Taiwanese adults with the TRIB1 GG genotype.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary to improve HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7543 participants, comprising 3472 men and 4071 women aged between 30 and 70 years, were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories—no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). Multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with higher HDL-C levels (β = 1.4077; p < 0.0001 and β = 5.6052; p = 0.0079, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30−70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (β = −5.705; p = 0.001) followed by lacto-ovo vegetarians (β = −3.900; p < 0.001) and former vegetarians (β = −0.329; p = 0.475). The test for trend was significant (p < 0.001). After categorization by exercise modalities, the β-value was −13.984 for strict vegetarians, −4.419 for lacto-ovo vegetarians, and −1.864 for former vegetarians, respectively (p < 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

Increased ventilation during exercise in polluted areas could trigger airway inflammation. We evaluated blood DNA methylation of the SOX2-promoter region in relation to exercise and PM2.5 in Taiwanese adults. Data of 948 participants aged 30−70 years were retrieved from the Taiwan Biobank Database (2008−2015) and the Air Quality Monitoring Database (2006−2011). PM2.5 was positively associated with SOX2-promoter methylation (β = 0.000216; p < 0.0001). The interaction between PM2.5 and exercise on SOX2-promoter methylation was significant (p = 0.0146). After stratification by exercise habits, PM2.5 was positively associated with SOX2 methylation in only individuals who did regular exercise (β = 0.0003490; p < 0.0001). After stratification by exercise habits and residential areas, SOX2-promoter methylation levels in those who lived in the southern area were higher for both the regular exercise (β = 0.00272; p = 0.0172) and no regular exercise groups (β = 0.002610 and p = 0.0162). SOX2-promoter methylation levels in those who lived in the northern area and did regular exercise were lower; β = -0.00314 (p = 0.0036). In conclusion, PM2.5 was positively associated with SOX2-promoter methylation in participants who did regular exercise. Living in the southern area was positively associated with SOX2-promoter methylation regardless of exercise habits.

Hyperlipidemia is one of the strong risk factors for ischemic heart disease. Using the Taiwan Biobank (TWB) database, we evaluated the risk of hyperlipidemia and its interaction with sex and rs688 polymorphism on the low-density lipoprotein receptor (LDLR) gene. Data collection in the biobank started in 2008 and is ongoing. Data analysis was performed on the participants’ data collected between 2008 and 2015. In general, 27.92% of the 9237 female participants and 32.65% of the 8690 male participants were identified with hyperlipidemia. Compared to the C/C genotype, C/T and T/T genotypes were not significant risk factors for hyperlipidemia (OR = 1.061, CI: 0.976−1.153 for C/T and OR = 1.052, CI: 0.845−1.309 for T/T genotype) in the general model. However, there was a significant interaction between sex and rs6888 on hyperlipidemia risk (p-interaction = 0.0321). With the male sex/CC genotype being the reference group, only the female sex/CT and T/T genotypes were closely associated with hyperlipidemia, with respective ORs of 1.153 (CI: 1.014−1.311) and 1.423 (CI: 1.056−1.917). Our data indicate that rs688 C/T and T/T genotypes may be associated with increased risk of hyperlipidemia in Taiwanese women. These findings may be relevant in lipid-modification therapy.

Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30−70 years were retrieved from the Taiwan Biobank Database (2008−2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (β = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.

Changes in concentrations of high-density lipoprotein cholesterol (HDL-C) are modified by several factors. We examined the relationship between aerobic exercise and HDL-C among different categories of body mass index (BMI) and waist-hip ratio (WHR) and the impact of rs1800588 variant in the hepatic lipase (LIPC) gene. We analyzed data from 6184 men and 8353 women aged 30−70 years. Participants were grouped into two WHR categories: Normal (0 < WHR < 0.9 for men and 0 < WHR < 0.8 for women) and abnormal (WHR ≥ 0.9 for men and WHR ≥ 0.8 for women). The BMI categories were: Underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24 kg/m2), overweight (24 ≤ BMI < 27 kg/m2), and obese (BMI ≥ 27 kg/m2). Multivariate linear regression models were used to investigate associations between HDL-C and exercise. Aerobic exercise was significantly associated with higher HDL-C (β = 1.18325; p < 0.0001) when compared with no exercise. HDL-C was significantly lower in persons with abnormal compared to those with normal WHR (β = −3.06689; p < 0.0001). Compared with normal weight, overweight and obese categories were associated with lower HDL-C, with β values of −4.31095 and −6.44230, respectively (p < 0.0001). Unlike rs1800588 CT and TT genotypes, associations between aerobic exercise and HDL were not significant among CC carriers no matter their BMI or WHR.

Low high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of global mortality. We aimed to determine the effect of coffee drinking and sex and their interaction, as well as rs1800588 and rs1800775 polymorphisms on HDL-C levels in Taiwanese adults. Data of 4262 men and 4813 women, aged 30−70 years, were retrieved from Taiwan Biobank. The interaction between sex and coffee drinking on HDL-C was significant (p = 0.0452). Coffee consumption was significantly associated with higher HDL-C levels in only women (β = 0.81679; p = 0.0246). However, rs1800588 and rs1800775 variants were significantly associated with HDL-C in both sexes. In women, β-values were 0.99080; p = 0.0059 and 3.16277; p < 0.0001 for rs1800588 CT and TT genotypes, respectively and −1.80954; p < 0.0001 and −2.81512; p < 0.0001 for rs1800775 AC and CC genotypes, respectively. In men, β-values were 1.32430; p < 0.0001 and 3.24976; p < 0.0001 for rs1800775 CT and TT genotypes, respectively and −1.96232; p < 0.0001 and −2.71536, p < 0.0001 for the AC and CC genotypes, respectively. In conclusion, coffee drinking was significantly associated with higher high-density lipoprotein (HDL) levels in women but not men after adjusting for confounders including rs1800588 (LIPC) and rs1800775 (CETP) variants.

The fat mass and obesity-associated (FTO) gene is a significant genetic contributor to polygenic obesity. We investigated whether physical activity (PA) modulates the effect of FTO rs3751812 on body mass index (BMI) among Taiwanese adults. Analytic samples included 10,853 Taiwan biobank participants. Association of the single-nucleotide polymorphism (SNP) with BMI was assessed using linear regression models. Physical activity was defined as any kind of exercise lasting 30 min each session, at least three times a week. Participants with heterozygous (TG) and homozygous (TT) genotypes had higher BMI compared to those with wild-type (GG) genotypes. The β value was 0.381(p < 0.0001) for TG individuals and 0.684 (p = 0.0204) for TT individuals. There was a significant dose-response effect among carriers of different risk alleles (p trend p < 0.0001). Among the active individuals, significant associations were found only with the TG genotype (β = 0.360, p = 0.0032). Inactive individuals with TG and TT genotypes had increased levels of BMI compared to those with GG genotypes: Their β values were 0.381 (p = 0.0021) and 0.950 (p = 0.0188), respectively. There was an interaction between the three genotypes, physical inactivity, and BMI (p trend = 0.0002). Our data indicated that increased BMI owing to genetic susceptibility by FTO rs3751812 may be reduced by physical activity.

The effects of genetic variants on the interaction between hyperlipidemia and sex have not been investigated among gout patients in Taiwan. Using Taiwan Biobank and the National Health Insurance Research Database (NHIRD), we examined hyperlipidemia, sex, and their relationship with gout among Taiwanese adults with the human leukocyte antigen B (HLA-B) genetic variants. Hyperlipidemia was present in 1437 patients with gout. Sex and hyperlipidemia had significant associations on gout risk, with hyperlipidemia showing a relatively stronger effect. Gout was present in men, with an odds ratio (OR) of 1.945 (95% confidence interval (CI) 1.568–2.411) compared to women, and in hyperlipidemic (OR = 4.032; 95% CI: 3.581–4.540) compared to non-hyperlipidemic patients. The interaction of sex and hyperlipidemia was significant for rs2523608 GG (p = 0.0402) and rs4713518 AA (p = 0.0003) genotypes. After stratification, hyperlipidemia remained a risk factor in women (OR = 4.735, 95% CI: 3.375–6.643) and men (OR = 3.640, 95% CI: 2.916–4.544) with rs2523608 GG genotype. The odds ratio in hyperlipidemic women and men with rs4713518 AA genotype was 7.454 (95% CI 5.103–10.888) and 3.585 (95% CI 2.854–4.503), respectively. Our study indicates that hyperlipidemia-sex interactions exist for gout risk in Taiwanese adults with rs2523608 GG and rs4713518 AA genotypes.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary in order to improve lipid HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7797 participants comprising 3559 men and 4238 women aged between 30 to 70 years were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories—no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). The multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with a higher HDL-C (β =1.3154; p p = 0.0027, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Complete surgical resection is recommended for early stage lung cancer, and adjuvant chemotherapy is given for stage IB to IIIA disease. No studies have examined the best timing to administer chemotherapy after surgery in lung cancer. This study was to investigate the optimal timing of adjuvant chemotherapy after surgical resection.Data collected from the Taiwan National Health Insurance Research Database between January, 2004 and December, 2010 were retrospectively analyzed. Patients with stage IB to IIIA lung cancer underwent complete surgical resection and adjuvant chemotherapy were included. A total of 1522 patients were included. The patients were divided into 4 groups according to the interval between surgery and chemotherapy: group 1, < 30 days; group 2, 30-45 days; group 3, 46-60 days; group 4 > 60 days. Univariate and multivariate regression analyses were used to identify prognostic factors for overall survival.The numbers of patients in groups 1, 2, 3, and 4 were 153, 161, 290, and 818, respectively. The 5-year survival rate was 41% in group 1, 48% in group 2, 50% in group 3, and 35% in group 4 (p

To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma.The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users.A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22-5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73-2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84-6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57-2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63-1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05-2.32; p = 0.261) for pneumonia+ TB, respectively.Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB)] are associated with lung cancer mortality. However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC) has not been well defined.Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database. Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010. Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB.During the study period, a total of 5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95% confidence interval (CI), 0.99-1.18], 1.04 (95% CI, 0.97-1.12), and 1.14 (95% CI, 1.00-1.31) for individuals with asthma, COPD, and TB, respectively. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23-1.97) and 1.11 (95% CI, 1.00-1.24) for individuals with asthma+COPD+TB and asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27-9.17) and 1.65 (95%CI, 1.10-2.47) for individuals with asthma+TB and asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00-1.97) and 1.25 (95%CI, 1.03-1.52) for individuals with asthma+ COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19 (95%CI, 005-0.77) for individuals with asthma.Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients. For female patients with early stage SqCC, pre-existing asthma decreased mortality. These patients deserve greater attention while undergoing cancer treatment.

This study aimed to investigate the association between herpes zoster (HZ) and human immunodeficiency virus (HIV). Data were retrieved from the Longitudinal Health Insurance Databases (LHID 2005 and 2010), Taiwan. The International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes were used to identify Hz from 2001-2004. Identification of HIV infection was from 2005-2010. The hazard ratios of HIV among herpes zoster infected and non-herpes zoster infected patients were estimated using multiple Cox proportional hazard model. In general, 19685 participants were identified with Hz. The HIV incidence rates (per 104 person-months) in herpes zoster infected and non-infected patients were 0.191(95% CI 0.130-0.280) and 0.079 (95% CI 0.074-0.084), respectively while the hazard ratio (HR) of HIV among infected individuals was 3.518 (95% CI 2.375-5.211). This study concludes that herpes zoster could be considered as a predictor of HIV infection especially among Asian populations, hence it is vital to test herpes zoster infected individuals for HIV antibodies.