Susceptibility to eye diseases in relation to age and kidney failure among Taiwanese adults.

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 < 50 years), kidney failure in all age groups was associated with a higher risk of cataract. The PORs; 95% CIs were 10.725; 4.227-27.211 for patients below 50 years, 28.487; 14.270-56.866 for those aged 50-60 years, and 43.183; 24.434-72.824 for those > 60 years. Combining cataract and age (reference: no cataract and age < 50 years), patients below 50 years had the highest risk of kidney failure (POR; 95% CI = 9.510; 3.722-24.297). CONCLUSIONS: Our study suggests that age and kidney failure may jointly contribute to eye diseases, particularly cataract. The association between cataract and kidney failure could be bidirectional, especially in individuals below 50 years. This significant bidirectional relationship underscores the need for screening patients with cataract for kidney failure and vice versa, particularly in younger adults.

Spine, hip, and femoral neck bone mineral density in relation to vegetarian type and status among Taiwanese adults.

We determined the association of vegetarian type and status with bone mineral density (BMD) Z-scores at the spine, hip, and femoral neck. Compared to non-vegetarians, current vegetarians, especially vegans, lacto-vegetarians, and lacto-ovo-vegetarians had lower Z-scores at multiple sites. Sole reliance on a vegetarian diet might be detrimental to the bone. PURPOSE: The impact of vegetarian diets on BMD is contentious. We determined the association of vegetarian type and status with the spine, hip, and femoral neck BMD Z-scores. METHODS: We analyzed data from 20,110 Taiwan Biobank volunteers. BMD was measured using dual-energy X-ray absorptiometry (DXA). The vegetarian status (non-, former, and current vegetarians) and type (non-vegetarians, ovo-vegetarians, lacto-vegetarians, lacto-ovo-vegetarians, and vegans) were determined using questionnaires. RESULTS: The participants consisted of 12,910 women and 7200 men, with a mean age of 55.5 years. Based on vegetarian status (reference: non-vegetarians), current vegetarians had significantly lower BMD Z-scores at the spine (unstandardized regression coefficient, B = - 0.195, p = 0.006), left hip (B = - 0.125, p = 0.008), and right hip (B = - 0.100, p = 0.027), respectively. Based on vegetarian status and type (reference: non-vegetarians), current vegans and non-vegans had notably lower BMD Z-scores at specific skeletal sites. For non-vegans, the BMD Z-scores were significant at the spine (B = -0.184, p = 0.010), left hip (B = - 0.124, p = 0.010), and left femoral neck (B = - 0.125, p = 0.012). For current vegans, however, the BMD Z-scores were significant only at the right hip (B = - 0.232; p = 0.028). Nonetheless, after stratifying vegetarian diet into more subgroups, current vegans exhibited a significant reduction in BMD Z-scores at the spine and right hip, with B-coefficients of - 0.326 and - 0.238, respectively. Current lacto-vegetarians also had significantly lower Z-scores (p < 0.05) at the spine (B = - 0.459), left hip (B = - 0.313), and right hip (B = - 0.214). Moreover, current lacto-ovo-vegetarians had significantly lower Z-scores at the spine (B = - 0.175) and left hip (B = - 0.115). CONCLUSION: Current vegetarians, particularly vegans, lacto-vegetarians, and lacto-ovo-vegetarians, demonstrated significantly lower BMD Z-scores at various skeletal sites compared to non-vegetarians. Sole reliance on a vegetarian diet might be detrimental to the bone.

Susceptibility to hypertension based on MTHFR rs1801133 single nucleotide polymorphism and MTHFR promoter methylation.

Background: The 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. Methods: We 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). Results: The distributions of hypertension and MTHFR promoter methylation quartiles (ß < 0.1338, 0.1338 ≤ ß < 0.1385, 0.1385 ≤ ß < 0.1423, and ß ≥ 0.1423 corresponding to

Risk of gout in Taiwan Biobank participants pertaining to their sex and family history of gout among first-degree relatives.

BACKGROUND: Family history of gout and sex are independently associated with gout. However, there is a paucity of research regarding the joint role of both factors in gout pathogenesis. Therefore, we assessed the independent and combined association of family history of gout and sex with gout. METHODS: Our analysis included 132,311 Taiwan Biobank (TWB)-enrolled individuals comprising 21,159 gout cases and 111,152 controls. We subcategorized the family history of gout as (1) both siblings and parents had gout), (2) only parents had gout, and (3) only siblings had gout. RESULTS: Generally, sex (men compared to women) and family history of gout were independently associated with a higher risk of gout. The odds ratio (OR); 95% confidence interval (CI) was 9.175; 8.801-9.566 for sex, and 2.306; 2.206-2.410 for family history. For the subcategories 'both siblings and had gout,' 'only parents had gout,' and 'only siblings had gout,' the odds ratios (ORs); 95% confidence intervals (CIs) were 4.944; 4.414-5.538, 2.041; 1.927-2.161, and 2.162; 2.012-2.323, respectively. The interaction between sex and family history was significant (p value = 0.0001). After stratification by sex, family history of gout remained significantly associated with a higher risk of gout in both sexes, even though the odds ratios were higher in men. For the subcategories 'both siblings and parents had gout,' 'only parent had gout,' and 'only siblings had gout,' the corresponding ORs; 95% CIs were 6.279; 5.243-7.520, 2.211; 2.062-2.371, and 2.148; 1.955-2.361 in men and 4.199; 3.566-4.945, 1.827; 1.640-2.035, and 2.093; 1.876-2.336 in women. After integrating sex and family history (reference: women with no family history), the highest risk of gout was observed in men who had at least one parent and sibling with a history of gout (OR; 95% CI 55.774; 46.360-67.101). CONCLUSION: Sex and family history of gout were independently and interactively associated with gout. Sex-wise, men had a higher risk of gout than women. Family history was associated with a higher risk of gout in both sexes, but men had a higher risk. Notably, men having both siblings and parents with gout had the highest risk of gout.

The association between vegetarian diet and varicose veins might be more prominent in men than in women.

Background: Varicose 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. Methods: The 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. Results: The 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. Conclusion: Women 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.

Association between ESR1 rs2234693 single nucleotide polymorphism and uterine fibroids in Taiwanese premenopausal and postmenopausal women.

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.

Cigarette smoking and PM2.5 might jointly exacerbate the risk of metabolic syndrome.

Background: Cigarette smoking and particulate matter (PM) with aerodynamic diameter < 2.5 µm (PM2.5) are major preventable cardiovascular mortality and morbidity promoters. Their joint role in metabolic syndrome (MS) pathogenesis is unknown. We determined the risk of MS based on PM2.5 and cigarette smoking in Taiwanese adults. Methods: The study included 126,366 Taiwanese between 30 and 70 years old with no personal history of cancer. The Taiwan Biobank (TWB) contained information on MS, cigarette smoking, and covariates, while the Environmental Protection Administration (EPA), Taiwan, contained the PM2.5 information. Individuals were categorized as current, former, and nonsmokers. PM2.5 levels were categorized into quartiles: PM2.5 ≤ Q1, Q1 < PM2.5 ≤ Q2, Q2 < PM2.5 ≤ Q3, and PM2.5 > Q3, corresponding to PM2.5 ≤ 27.137, 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 38.205 µg/m3. Results: The prevalence of MS was significantly different according to PM2.5 exposure (p-value = 0.0280) and cigarette smoking (p-value < 0.0001). Higher PM2.5 levels were significantly associated with a higher risk of MS: odds ratio (OR); 95% confidence interval (CI) = 1.058; 1.014-1.104, 1.185; 1.134-1.238, and 1.149; 1.101-1.200 for 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 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 < 0.0001. The interaction between both exposures regarding MS was significant (p-value = 0.0157). Stratification by cigarette smoking revealed a significant risk of MS due to PM2.5 exposure among nonsmokers: OR (95% CI) = 1.074 (1.022-1.128), 1.226 (1.166-1.290), and 1.187 (1.129-1.247) for 27.137 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 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 < PM2.5 ≤ 32.589, 32.589 < PM2.5 ≤ 38.205, and PM2.5 > 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). Conclusion: PM2.5 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.

Associations Between Body Mass Index, WNT16 rs2908004 and Osteoporosis: Findings from Taiwan Biobank.

Purpose: Osteoporosis is a degenerative disease that affects women and men of all races. We studied the association between body mass index (BMI), rs2908004 polymorphism of the WNT16 gene, and osteoporosis using data from Taiwan Biobank (TWB). Patients and Methods: We analyzed data from 10,942 subjects aged 30 to 70. We defined osteoporosis based on a mean T-score of -2.5 and below in the hip. Body mass index was classified following the guidelines of the Health Promotion Administration. Imputation was carried out using the IMPUTE2 (v2.3.1) program. Multiple logistic regression was used for analysis. The odds ratios (ORs) and 95% confidence interval (CI) for osteoporosis were determined. Results: In the multivariate regression model, variant rs2908004 had a significant association with osteoporosis. That is, the rs2908004-GA+AA genotype was associated with lower osteoporosis risk than the GG genotype (OR, 0.651; 95% CI = 0.544 to 0.780). Compared to normal-weight, underweight was significantly associated with a higher risk of osteoporosis (OR, 6.517; 95% CI = 4.624 to 9.186) while overweight and obesity were protective (OR, 0.176; 95% CI = 0.140 to 0.221 and 0.057; 95% CI = 0.039 to 0.083, respectively). There was an interaction between rs2908004 and BMI (p = 0.0148). Subgroup analyses (using rs2908004-GG/normal-weight as the reference group) indicated ORs of 7.66 (95% CI = 5.153 to 11.394) in the rs2908004-GG/underweight group and 3.002 (95% CI = 1.509 to 5.974) in the rs2908004-GA+AA/underweight group (95% CI = 1.509 to 5.974). Odds ratios were substantially lower in rs2908004-GG/obese, rs2908004-GG/overweight, GA+AA/normal-weight, rs2908004-GA+AA/overweight, and rs2908004-GA+AA/obese groups, respectively. Conclusion: According to our study, underweight was associated with an increased risk of osteoporosis irrespective of WNT16 rs2908004 genotypes, while overweight and obesity were associated with a lower risk.

ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals.

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 < 0.0001) and had a higher body mass index (BMI) than the stroke-free individuals. The risk of ischemic stroke was significantly higher among subjects with the ALDH7A1 rs12514417 TG + GG genotype who also consumed alcohol at least 150 ml/week (odds ratio (OR), 1.79; 95% confidence interval (CI), 1.18-2.72). We found that rs12514417 genotype and alcohol consumption (at least 150 ml/week) showed a significant interaction (p for interaction = 0.0266). Stratification based on alcohol exposure and ALDH7A1 rs12514417 genotypes indicated that ischemic stroke risk was significantly higher among alcohol drinkers with the TG + GG genotype than in those with the TT genotype (OR, 1.64, 95% CI: 1.15-2.33). CONCLUSION: Our study suggests that the combination of ALDH7A1 rs12514417 TG + GG genotype and alcohol exposure of at least 150 ml/week may increase the risk of ischemic stroke in Taiwanese adults.

Effects of aerobic and resistance exercise on glycosylated hemoglobin (HbA1c) concentrations in non-diabetic Taiwanese individuals based on the waist-hip ratio.

BACKGROUND: Glycosylated 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). METHODS: We conducted this study based on TWB data collected from 90,958 individuals between 2008 and 2019. We estimated the Beta (ß) coefficient and 95% confidence intervals (CI) for HbA1c using multivariate regression models. RESULTS: Based on the multivariate analysis, lower HbA1c levels were associated with both resistance exercise (ß-coefficient = -0.027, 95% CI -0.037 to -0.017) and aerobic exercise (ß-coefficient = 0.018, 95% CI, -0.023 to -0.013). Higher HbA1c levels were associated with abnormal WHR compared to normal WHR (ß-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 (ß = -0.121, 95% CI, -0.132 to -0.109). CONCLUSIONS: We found that normal resistance exercise, coupled with a normal WHR was significantly associated with lower HbA1c levels among non-diabetic individuals in Taiwan.

Risk of uterine leiomyoma based on BET1L rs2280543 single nucleotide polymorphism and vegetarian diet.

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.

Interaction between a diabetes-related methylation site (TXNIP cg19693031) and variant (GLUT1 rs841853) on fasting blood glucose levels among non-diabetics.

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 (ß) 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 ß < 0.738592 (< Q1), 0.738592 ≤ 0.769992 (Q1-Q2), 0.769992 ≤ 0.800918 (Q2-Q3), and ß ≥ 0.800918 (≥ Q3). FBG increased with decreasing cg19693031 methylation levels in a dose-response manner (ptrend = 0.005). The ß-coefficient was - 0.0236 (p = 0.965) for Q2-Q3, 1.0317 (p = 0.058) for Q1-Q2, and 1.3336 (p = 0.019 for < Q1 compared to the reference quartile (≥ Q3). The genetic variant rs841853 was not significantly associated with FBG. However, its interaction with cg19693031 methylation was significant (p-value = 0.036). Based on stratification by rs841853 genotypes, only the CC group retained the inverse and dose-response association between FBG and cg19693031 methylation. The ß (p-value) was 0.8082 (0.255) for Q2-Q3, 1.6930 (0.022) for Q1-Q2, and 2.2190 (0.004) for < Q1 compared to the reference quartile (≥ Q3). The ptrend was 0.002. CONCLUSION: Summarily, methylation at cg19693031 was inversely associated with fasting blood glucose in a dose-dependent manner. The inverse association was more prominent in rs841853-CC individuals, suggesting that rs841853 could modulate the association between cg19693031 methylation and FBG. Our results suggest that genetic variants may be involved in epigenetic mechanisms associated with FBG, a hallmark of diabetes. Therefore, integrating genetic and epigenetic data may provide more insight into the early-onset of diabetes.

Risk of gallstones based on ABCG8 rs11887534 single nucleotide polymorphism among Taiwanese men and women.

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 < 0.05, the baseline genotypes and gallstone status between men and women were not significantly different. The risk of gallstones was higher in participants having the GC + CC compared to the GG genotype: odds ratio (OR); 95% confidence interval (CI) = 1.698; 1.240-2.325), but was lower in men compared to women (OR = 0.763; 95% CI = 0.638-0.913). Compared to men with the rs11887534 GG genotype, women with the GG and GC + CC genotypes had a higher risk of gallstone (OR; 95% CI = 1.304; 1.087-1.565 for GG and 2.291; 1.514-3.467 for GC + CC). The positive association between GC + CC and gallstones was retained after we restricted the analysis to the female participants (OR; 95% CI = 1.789 = 1.208-2.648). Hormone use was associated with an elevated risk of gallstones (OR; 95% CI = 1.359; 1.107-1.668). Relative to GG and no hormone use, we found a significantly high risk among hormone users with the GC + CC genotype (OR; 95% CI = 3.596; 1.495-8.650). CONCLUSIONS: The rs11887534 GC + CC genotype was independently associated with a higher risk of gallstones. This risk was much higher among women, especially those who used hormones for various gynecological purposes.

Risk of HBV infection among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan.

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.

Interactive Association Between CYP2C9 rs2860905 Polymorphism and Atrial Fibrillation on Ischemic Stroke in Taiwan Biobank Participants.

PURPOSE: Ischemic stroke accounts for approximately 85% of all strokes. Risk factors include atrial fibrillation, metabolic disorders, and genetic and lifestyle factors. There is limited evidence to support the association between atrial fibrillation and the risk of ischemic stroke based on genetic variants. We assessed the relationship between ischemic stroke and atrial fibrillation among participants in Taiwan Biobank (TWB) based on the rs2860905 variant of the cytochrome P450 Family 2 Subfamily C Member 9 (CYP2C9) gene. MATERIALS AND METHODS: Using logistic regression analysis, we estimated the odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke among 17,726 biobank adults recruited from 2008 through 2015. RESULTS: Of the eligible participants (n = 17,726), 906 were identified with ischemic stroke. Atrial fibrillation was positively associated with ischemic stroke (OR=3.70; 95% CI, 2.21-6.20), whereas the rs2860905 variant was not. The OR for ischemic stroke among those with GA/AA genotype was 1.00 (95% CI, 0.82-1.22) compared to those with the GG genotype. Based on the genotype-stratified analysis, the OR for ischemic stroke was 4.68 (95% CI, 2.70-8.09) among individuals with GG genotype who had atrial fibrillation compared to those who did not. CONCLUSION: These results demonstrate that the GG genotype of the CYP2C9 rs2860905 variant appears to enhance the risk of ischemic stroke among adults in Taiwan. It could be essential to factor this genotype-specific contributor to ischemic stroke into clinical and experimental investigations of the disease in Taiwan.

Association between hypertension and coffee drinking based on CYP1A2 rs762551 single nucleotide polymorphism in Taiwanese.

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.

Peripheral Vascular Disease Susceptibility Based on Diabetes Mellitus and rs17367504 Polymorphism of the MTHFR Gene.

PURPOSE: Peripheral vascular disease (PVD) is a life-threatening condition affecting the lower extremities. Common risk factors include type 2 diabetes (T2D), hypertension, dyslipidemia, smoking, and older age. There is a little-documented research on the genetic basis of the disease in Taiwan. We examined the impact of T2D and the blood pressure-associated rs17367504 variant of the Methylenetetrahydrofolate reductase (MTHFR) gene on PVD risk. MATERIALS AND METHODS: In this population-based association study, we linked data from 8992 participants in Taiwan Biobank (TWB) to their medical records in the National Health Insurance Research Database (NHIRD). Participants were 30 to 70 years old at recruitment and included those assessed between 2008 and 2015. We tested for association of PVD with rs17367504 and T2D using multiple logistic regression models. The rs17367504 variant was assessed using the Axiom-Taiwan Biobank Array Plate (TWB chip: Affymetrix, Inc., Santa Clara, CA, USA). RESULTS: Among cases with T2D (n = 1294), 158 (12.21%) were identified with PVD. T2D was associated with PVD (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.21-1.91; p<0.001) whereas rs17367504 variant was not (OR, 0.96; CI, 0.76-1.21; p = 0.728 in AG/GG compared to AA homozygotes). However, T2D and rs17367504 had an interactive effect on PVD (p for interaction = 0.0076). Results from our stratified analyses displayed OR of 1.75 (CI, 1.35-2.26; p<0.001) in AA individuals with DM and 0.94 (CI, 0.56-1.58; p = 0.811) in AG+GG individuals with T2D. Using the AA genotype and no T2D as the reference group, the respective OR of PVD was 1.77 (CI, 1.38-2.28; p<0.001) in AA individuals with T2D; 1.18 (CI, 0.91-1.55; p = 0.215) in AG+GG individuals with no T2D, and 1.03 (CI, 0.66-1.60; p = 0.892) in AG+GG individuals with T2D . CONCLUSION: We found that type 2 diabetes was associated with increased risk of peripheral vascular disease, particularly in AA genotype carriers of the rs17367504 variant in Taiwan.

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke.

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 < 0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC + CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92-12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction = 0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC + CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19-16.52). CONCLUSIONS: Our study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

Risk of gout among Taiwanese adults with ALDH-2 rs671 polymorphism according to BMI and alcohol intake.

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.

Association of Age and Sex with Metabolic Syndrome in Taiwanese Adults.

OBJECTIVE: This study aimed to investigate the association of age and sex with metabolic syndrome (MS) in Taiwanese adults. METHODS: We extracted information of 4307 men and 4783 women aged 30-70 from the Taiwan Biobank. RESULTS: The interaction between age and sex on MS was significant (p-value = 0.0001). After stratification by sex, men and women aged 50-70 years (reference: 30≤age<50 years) had a higher risk of MS. The odds ratio (OR), 95% confidence interval (CI) was 2.316, 1.936-2.772 in men and 3.101, 2.561-3.754 in women. After stratification by age, men aged 50-70 years had a lower risk of MS compared to women (OR, 95% CI = 0.713, 0.598-0.851). CONCLUSION: The interaction between age and sex on MS was significant. Sex-wise, both men and women aged 50-70 years had a higher likelihood of MS. Age-wise, men aged 50-70 years had a lower risk of MS compared to women.