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Chun-Sheng Hsu,1– 4 Shin-Tsu Chang,1,5,6 Oswald Ndi Nfor,2 Kuan-Jung Lee,2 Chien-Chang Ho,7,8 Chuan-Ching Liu,1 Shiuan-Shinn Lee,2 Yung-Po Liaw2,9 1Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung City, 40201, Taiwan; 2Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung City, 40201, Taiwan; 3School of Medicine, National Defense Medical Center, Taipei City, 11490, Taiwan; 4College of Medicine, National Chung Hsing University, Taichung City, 402, Taiwan; 5Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, School of Medicine, National Defense Medical Centre, Taipei City, 11490, Taiwan; 6Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung City, 813414, Taiwan; 7Department of Physical Education, Fu Jen Catholic University, New Taipei, 24205, Taiwan; 8Research and Development Center for Physical Education, Health, and Information Technology, Fu Jen Catholic University, New Taipei, 24205, Taiwan; 9Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, TaiwanCorrespondence: Yung-Po Liaw; Shiuan-Shinn LeeDepartment of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sec. 1 Jianguo N. Road, Taichung City, 40201, TaiwanTel +886 424730022 ext. 11838; +886 424730022 ext.12185Fax +886 423248179Email Liawyp@csmu.edu.tw; shinn@csmu.edu.twPurpose: The Lipoprotein lipase (LPL) gene is a significant contributor to dyslipidemia. It has shown associations with several conditions including atherosclerosis, obesity, and metabolic syndrome (MetS). We assessed the interactive association between MetS and rs3779788 of the LPL gene based on aerobic exercise.Materials and Methods: Data were available for 7532 Taiwan Biobank (TWB) participants recruited between 2008 and 2016. We used multiple logistic regression to determine the odds ratios (OR) for MetS and their 95% confident intervals (C.I.). Potential variables included LPL rs3779788, aerobic exercise, sex, age, education, marital status, body mass index (BMI), smoking, alcohol consumption, midnight snacking, vegetarian diet, coffee, dietary fat, and tea drinking.Results: Aerobic exercise was protective against MetS (OR, 0.858; 95% C.I., 0.743– 0.991). Compared to CC/CT genotype, the OR for developing MetS was 0.875, (95% C.I., 0.571– 1.341) in TT individuals. The test for interaction was significant for the rs3779788 variant and aerobic exercise (p = 0.0484). In our group analyses, the OR for MetS was 0.841 (95% C.I., 0.727– 0.974) in CC/CT and 4.076 (95% C.I., 1.158– 14.346) in TT individuals who did aerobic exercise compared to those who did not.Conclusion: Our study indicated that aerobic exercise improved metabolic syndrome in Taiwanese adults with rs3779788 CC/CT genotype relative to those with TT genotype.Keywords: polymorphisms, variant, physical activity, metabolic disorders

Aims To develop an artificial intelligence-based approach with multi-labelling capability to identify both ST-elevation myocardial infarction (STEMI) and 12 heart rhythms based on 12-lead electrocardiograms (ECGs). Methods and results We trained, validated, and tested a long short-term memory (LSTM) model for the multi-label diagnosis of 13 ECG patterns (STEMI + 12 rhythm classes) using 60 537 clinical ECGs from 35 981 patients recorded between 15 January 2009 and 31 December 2018. In addition to the internal test above, we conducted a real-world external test, comparing the LSTM model with board-certified physicians of different specialties using a separate dataset of 308 ECGs covering all 13 ECG diagnoses. In the internal test, the area under the curves (AUCs) of the LSTM model in classifying the 13 ECG patterns ranged between 0.939 and 0.999. For the external test, the LSTM model for multi-labelling of the 13 ECG patterns evaluated by AUC was 0.987 ± 0.021, which was superior to those of cardiologists (0.898 ± 0.113, P Conclusions We demonstrated the usefulness of an LSTM model in the multi-labelling detection of both rhythm classes and STEMI in competitive testing against board-certified physicians. This AI tool exceeding the cardiologist-level performance in detecting STEMI and rhythm classes on 12-lead ECG may be useful in prioritizing chest pain triage and expediting clinical decision-making in healthcare.

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&ndash, 70 years were retrieved from the Taiwan Biobank Database (2008&ndash, 2015) and the Air Quality Monitoring Database (2006&ndash, 2011). PM2.5 was positively associated with SOX2-promoter methylation (&beta, = 0.000216, p &lt, 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 (&beta, = 0.0003490, 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 (&beta, = 0.00272, p = 0.0172) and no regular exercise groups (&beta, = 0.002610 and p = 0.0162). SOX2-promoter methylation levels in those who lived in the northern area and did regular exercise were lower, &beta, = -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.

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&ndash, 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 (&beta, = &minus, 5.705, p = 0.001) followed by lacto-ovo vegetarians (&beta, 3.900, p &lt, 0.001) and former vegetarians (&beta, 0.329, p = 0.475). The test for trend was significant (p &lt, 0.001). After categorization by exercise modalities, the &beta, value was &minus, 13.984 for strict vegetarians, &minus, 4.419 for lacto-ovo vegetarians, and &minus, 1.864 for former vegetarians, respectively (p &lt, 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.

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&ndash, 70 years. Participants were grouped into two WHR categories: Normal (0 &lt, WHR &lt, 0.9 for men and 0 &lt, 0.8 for women) and abnormal (WHR &ge, 0.9 for men and WHR &ge, 0.8 for women). The BMI categories were: Underweight (BMI &lt, 18.5 kg/m2), normal weight (18.5 &le, BMI &lt, 24 kg/m2), overweight (24 &le, 27 kg/m2), and obese (BMI &ge, 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 (&beta, = 1.18325, p &lt, 0.0001) when compared with no exercise. HDL-C was significantly lower in persons with abnormal compared to those with normal WHR (&beta, = &minus, 3.06689, 0.0001). Compared with normal weight, overweight and obese categories were associated with lower HDL-C, with &beta, values of &minus, 4.31095 and &minus, 6.44230, respectively (p &lt, 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&ndash, 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 (&beta, = 0.81679, p = 0.0246). However, rs1800588 and rs1800775 variants were significantly associated with HDL-C in both sexes. In women, &beta, values were 0.99080, p = 0.0059 and 3.16277, p &lt, 0.0001 for rs1800588 CT and TT genotypes, respectively and &minus, 1.80954, 0.0001 and &minus, 2.81512, 0.0001 for rs1800775 AC and CC genotypes, respectively. In men, &beta, values were 1.32430, 0.0001 and 3.24976, 0.0001 for rs1800775 CT and TT genotypes, respectively and &minus, 1.96232, 2.71536, p &lt, 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.

Increased levels of high-density lipoprotein cholesterol (HDL-C) can improve endothelial function. This may help reduce cardiovascular risks and mortality. Evidence has been provided on the association between cardiometabolic traits, such as HDL-C and exercise modalities. However, there is the absence of studies investigating this association in Taiwan. We assessed the relationship between exercise type and HDL-C among Taiwanese adults. Data were collected from Taiwan Biobank (TWB), a national biomedical research database that contains the genetic information of ethnic Taiwanese residents gathered from 2008 to 2016. We enrolled 24,856 participants aged 30 to 70 years who completed a questionnaire about their recent health behaviors including smoking, drinking, and exercise. Regular exercise was categorized as non-aerobic exercise (separated as weight training, ball game, and mixed exercise) and strict aerobic exercise. Linear regression models were used to assess the effects of exercise in a questionnaire-based manner. After multivariate adjustments, HDL-C was positively associated with aerobic (&beta, = 1.33748, p &lt, 0.0001) and non-aerobic (&beta, = 2.56210, p &lt, 0.0001) exercise. Positive associations were also found for resistance training (&beta, = 4.01828, p = 0.0020), ballgame (&beta, = 2.43815, p = 0.0001), and mixed exercise (&beta, = 2.47021, p &lt, 0.0001). This study demonstrated that both aerobic and non-aerobic exercise have positive effects on HDL-C among Taiwanese adults. Among the non-aerobic exercise groups, resistance training had the greatest effect.

DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008–2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30–70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β = − 0.01003, P = 0.009 and β = − 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease.

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

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&mdash, 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 (&beta, =1.3154, p &lt, 0.0001 and &beta, = 6.5954, 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.

Spearman correlation between PM2.5 concentrations (Îźg/m3) and mean methylation levels (beta values) in the northern, north-central, central, and southern areas. The methylation beta values decrease as PM2.5 levels increase. (DOCX 40 kb)

Table S1. Multiple linear regression showing beta coefficients of SOX2 methylation both in and outside the promoter region. Table S2. Multiple linear regression showing beta coefficients of SOX2 methylation in the exon. Table S3. Multiple linear regression showing beta coefficients of SOX2 methylation in the 3UTR region. Table S4. Multiple linear regression showing beta coefficients of KRAS promoter methylation. (DOCX 22 kb)

AHRR CpG sites significantly associated with PM2.5. (DOCX 20 kb)

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&mdash, 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 (&beta, = 1.4077, p &lt, 0.0001 and &beta, = 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 DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. Methods Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008–2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30–70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. Results Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β = − 0.01003, P = 0.009 and β = − 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. Conclusion Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease. Electronic supplementary material The online version of this article (10.1186/s13148-019-0662-9) contains supplementary material, which is available to authorized users.

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&ndash, 70 years were retrieved from the Taiwan Biobank Database (2008&ndash, 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 &plusmn, 0.00437 and 0.5375 &plusmn, 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 (&beta, = 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.

CDKAL1 rs10946398 is a type 2 diabetes (T2D)-associated variant. It is a new body mass index (BMI)-associated variant in Asian populations. We investigated the association between rs10946398 and T2D among 9908 participants aged 30–70 years based on BMI: normal weight; 18.5 ≤ BMI 2, overweight; 24 ≤ BMI 2, and obesity; BMI ≥27 kg/m2. The CC genotype conferred a higher risk of T2D than the CA genotype. The odds ratios (ORs) were 1.83; 95% confidence interval (CI) 1.49–2.26 and 1.20; 95% CI 1.02–1.40, respectively. The C allele was the significant risk allele compared with A allele (OR = 1.32; 95% CI 1.19–1.47). For normal, overweight and obese participants with CC genotype, the ORs were respectively 1.69; 95% CI 1.02–2.81, 2.34; 95% CI 1.50–3.66, and 1.58; 95% CI 1.02–2.45 among men and 1.22; 95% CI 0.67–2.22, 2.42; 95% CI 1.30–4.52, and 2.3; 95% CI 1.19–4.50 among women. The C allele ORs were higher in obese and overweight women. In conclusion, the rs10946398 CC/CA genotypes, as well as the C allele increased the risk of T2D. The ORs were higher in women who were overweight and obese than in those with normal weight. Nonetheless, significant results were prominent only among those with CC genotype and C allele.