Publications by authors named "Tangchun Wu"

314 Publications

Associations of plasma metal concentrations with incident dyslipidemia: Prospective findings from the Dongfeng-Tongji cohort.

Chemosphere 2021 Jul 9;285:131497. Epub 2021 Jul 9.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Metal exposures are ubiquitous around the world, while it is lack of prospective studies to evaluate the associations of exposure to multiple metal/metalloids with incident dyslipidemia. A total of 2947 participants without dyslipidemia at baseline were included in the analyses. We utilized inductively coupled plasma mass spectrometry to measure the baseline plasma metal concentrations. Unconditional logistic regression models were applied to estimate the relations between plasma metals and risk of incident dyslipidemia, and principal component analysis was performed to extract principal components of metals. During 5.01 ± 0.31 years of follow-up, 521 subjects were diagnosed with incident dyslipidemia. After multivariable adjustment, the odds ratios (ORs) of dyslipidemia comparing the highest quartiles to the lowest were 1.58 (95% CI: 1.20, 2.08; P = 0.001) for aluminum, 1.34 (95% CI: 1.03, 1.75; P = 0.03) for arsenic, 1.44 (1.09, 1.91; P = 0.03) for strontium, and 1.47 (95% CI: 1.09, 2.00; P = 0.005) for vanadium. The four metals also showed significant associations with the subtypes of dyslipidemia, including low HDL-C and high LDL-C. The first principal component, which mainly represented aluminum, arsenic, barium, lead, vanadium, and zinc, was associated with increased risk of incident dyslipidemia, and the adjusted OR was 1.40 (95% CI: 1.07, 1.84; P = 0.02) comparing extreme quartiles. The study indicated that elevated plasma aluminum, arsenic, strontium, and vanadium concentrations were associated with a higher incidence of dyslipidemia. These findings highlight the importance of controlling metal exposures for dyslipidemia prevention.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131497DOI Listing
July 2021

Exposure to polycyclic aromatic hydrocarbons, DNA methylation and heart rate variability among non-current smokers.

Environ Pollut 2021 Jul 10;288:117777. Epub 2021 Jul 10.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with heart rate variability (HRV) reduction, a widely used marker of cardiovascular autonomic dysfunction. The role of DNA methylation in the relationship between PAHs exposure and decreased HRV is largely unknown. This study aims to explore epigenome-wide DNA methylation changes associated with PAHs exposure and further evaluate their associations with HRV alternations among non-current smokers. We measured 10 mono-hydroxylated PAHs (OH-PAHs) in urine and DNA methylation levels in blood leukocytes among participants from three panels of Chinese non-current smokers (152 in WHZH, 99 in SY, and 53 in COW). We conducted linear regression analyses between DNA methylation and OH-PAHs metabolites with adjustment for age, gender, body mass index, drinking, blood cell counts, and surrogate variables in each panel separately, and combined the results by using inverse-variance weighted fixed-effect meta-analysis to obtain estimates of effect size. The median value of total OH-PAHs ranged from 0.92 × 10 in SY panel (62.6% men) to 13.82 × 10 μmol/mmol creatinine in COW panel (43.4% men). The results showed that methylation levels of cg18223625 (COL20A1) and cg07805771 (SLC16A1) were significantly or marginally significantly associated with urinary 2-hydroxynaphthalene [β(SE) = 0.431(0.074) and 0.354(0.068), FDR = 0.016 and 0.056, respectively], while methylation level of cg09235308 (PLEC1) was positively associated with urinary total OH-PAHs [β(SE) = 0.478(0.079), FDR = 0.004]. Hypermethylations of cg18223625, cg07805771, and cg09235308 were inversely associated with HRV indices among the WHZH and COW non-current smokers. However, we did not observe significant epigenome-wide associations for the other 9 urinary OH-PAHs. These findings provide new evidence that PAHs exposure is linked to differential DNA methylation, which may help better understand the influences of PAHs exposure on HRV alternations.
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http://dx.doi.org/10.1016/j.envpol.2021.117777DOI Listing
July 2021

Association of fine particulate matter air pollution and its constituents with lung function: The China Pulmonary Health study.

Environ Int 2021 Jun 26;156:106707. Epub 2021 Jun 26.

Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing, China; National Center of Gerontology, Beijing, China.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of exhaled FVC (FEF) associated with an interquartile range (IQR) change of PM or its constituents. Residential annual PM levels varied from 26 μg/m to 92 μg/m (average: 53 μg/m). An IQR increase of PM concentrations was associated with lower FEV (19.82 mL, 95% CI: 11.30-28.33), FVC (17.45 mL, 95% CI: 7.16-27.74), PEF (86.64 mL/s, 95% CI: 59.77-113.52), and FEF (31.93 mL/s, 95% CI: 16.64-47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.
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http://dx.doi.org/10.1016/j.envint.2021.106707DOI Listing
June 2021

Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection.

Cell Mol Immunol 2021 07 7;18(7):1832-1834. Epub 2021 Jun 7.

Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1038/s41423-021-00708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182358PMC
July 2021

Metabolome-Genome-Wide Association Study (mGWAS) Reveals Novel Metabolites Associated with Future Type 2 Diabetes Risk and Susceptibility Loci in a Case-Control Study in a Chinese Prospective Cohort.

Glob Chall 2021 Apr 23;5(4):2000088. Epub 2021 Mar 23.

CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China.

In a Chinese prospective cohort, 500 patients with new-onset type 2 diabetes (T2D) within 4.61 years and 500 matched healthy participants are selected as case and control groups, and randomized into discovery and validation sets to discover the metabolite changes before T2D onset and the related diabetogenic loci. A serum metabolomics analysis reveals that 81 metabolites changed significantly before T2D onset. Based on binary logistic regression, eight metabolites are defined as a biomarker panel for T2D prediction. Pipecolinic acid, carnitine C14:0, epinephrine and phosphatidylethanolamine 34:2 are first found associated with future T2D. The addition of the biomarker panel to the clinical markers (BMI, triglycerides, and fasting glucose) significantly improves the predictive ability in the discovery and validation sets, respectively. By associating metabolomics with genomics, a significant correlation ( < 5.0 × 10) between eicosatetraenoic acid and the FADS1 (rs174559) gene is observed, and suggestive correlations ( < 5.0 × 10) between pipecolinic acid and CHRM3 (rs535514), and leucine/isoleucine and WWOX (rs72487966) are discovered. Elevated leucine/isoleucine levels increased the risk of T2D. In conclusion, multiple metabolic dysregulations are observed to occur before T2D onset, and the new biomarker panel can help to predict T2D risk.
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http://dx.doi.org/10.1002/gch2.202000088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025395PMC
April 2021

Effect of GLP-1/GLP-1R on the Polarization of Macrophages in the Occurrence and Development of Atherosclerosis.

Mediators Inflamm 2021 27;2021:5568159. Epub 2021 Mar 27.

Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, China.

Aims: To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis.

Methods: Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1, IL-6, IL-10, TNF, and IL-12p70.

Results: GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group ( < 0.05). There was no difference in the percentage of total, M1 or M2 macrophages ( > 0.05). Concentration of IL-8 in the HC group was higher than that in the CHD group ( < 0.05). There is no significant difference in the cytokine IL-1, IL-6, IL-10, TNF, and IL-12p70 in the two groups ( > 0.05). After controlling for potential confounders including age, gender, smoking status (S.S.), drinking status (D.S.), HR, SBP, DBP, PP, TC, TG, HDL-C, LDL-C, GHbA1c, M, M1, M2, GLP-1R_M, GLP-1R_M1, GLP-1R_M2, IL-8, IL-1, IL-6, IL-10, TNF, and IL-12p70 by multiple linear regression, decreasing Gensini Score was significantly associated with increased percentage of M1 macrophage.

Conclusion: GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis.
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http://dx.doi.org/10.1155/2021/5568159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019627PMC
March 2021

Road traffic and air pollution: Evidence from a nationwide traffic control during coronavirus disease 2019 outbreak.

Sci Total Environ 2021 Aug 19;781:146618. Epub 2021 Mar 19.

Department of Occupational and Environmental Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, China. Electronic address:

Existing estimations of air pollution from automobile sources are based on either experiments or small-scale governmental interventions. China's nationwide traffic control during the coronavirus disease 2019 outbreak provided us a unique opportunity to assess the direct dose-effect relationship between vehicle density and air pollution. We found that, during the coronavirus disease 2019 outbreak, the nationwide reduced air pollution (except for O) could be largely explained by traffic control measures. During the traffic control period, every doubling of vehicle density was associated with a decrease of 4.2 (2.0, 6.4) μg/m in PM, 5.5 (2.9, 8.1) μg/m in PM, 1.5 (0.9, 2.0) μg/m in NO, and 0.04 (0.02, 0.07) mg/m in CO comparing cities with different vehicle densities. Similarly, for every 10% increase in the truck proportion, PM decreased by 12.3 (4.1, 20.6) μg/m, PM decreased by 14.3 (4.6, 23.9) μg/m, and CO decreased by 0.14 (0.05, 0.23) mg/m. Moreover, the associations between vehicle density and reduction in PM, PM, and CO during the traffic control period were stronger and showed near-complete linearity in cities with low green coverage rate (All P < 0.05 for interaction). According to our estimation, PM emissions from every doubling of vehicle density can lead to over 8000 excess deaths per year, 66% of which were caused by cardiopulmonary diseases. This natural experiment study is the first to observe the dose-effect relationship between on-road traffic and traffic-generated air pollution, as well as the mitigating effect of urban greening. Findings provide key evidence to the assessment and control of traffic-generated air pollution and its public health impact.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146618DOI Listing
August 2021

Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities.

BMJ 2021 03 24;372:n534. Epub 2021 Mar 24.

Department of Environmental Health, Portuguese National Institute of Health, Porto, Portugal.

Objective: To evaluate the short term associations between nitrogen dioxide (NO) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol.

Design: Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis.

Setting: 398 cities in 22 low to high income countries/regions.

Main Outcome Measures: Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018.

Results: On average, a 10 μg/m increase in NO concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM and PM, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities.

Conclusions: This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO.
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http://dx.doi.org/10.1136/bmj.n534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988454PMC
March 2021

Past Shift Work and Incident Coronary Heart Disease in Retired Workers: A Prospective Cohort Study.

Am J Epidemiol 2021 Mar 17. Epub 2021 Mar 17.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Present shift work has been associated with coronary heart disease (CHD) among employed workers, but it remains unclear whether shift work in the past is still associated with CHD in retired workers. We recruited 21,802 retired workers in Shiyan, China in 2008-2010 and 2013, and followed them up for CHD events to December 31, 2018. Retired workers with longer duration of past shift work had higher CHD risks (hazard ratios for those with ≤5.0, 5.25 to 10.0, 10.5 to 20.0, and >20.0 years of past shift work were 1.05 (95% confidence interval: 0.94, 1.16), 1.08 (0.94, 1.25), 1.23 (1.07, 1.42), and 1.28 (1.08, 1.51)). The association was substantially higher among services or sales workers than among manufacturing or manual labor workers (hazard ratio for every 5-year increase in past shift work, 1.11 (95% confidence interval: 1.05, 1.16) versus 1.02 (0.98, 1.06)). Moreover, the risk was lower among those who were physically active than their inactive counterparts (P for interaction, 0.019). Longer duration of past shift work was associated with higher risk of incident CHD among retired workers, especially those from services or sales sectors. Physical exercise might be beneficial in reducing the excess risk.
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http://dx.doi.org/10.1093/aje/kwab074DOI Listing
March 2021

Prospective Study on Plasma MicroRNA-4286 and Incident Acute Coronary Syndrome.

J Am Heart Assoc 2021 Mar 10;10(6):e018999. Epub 2021 Mar 10.

Department of Occupational and Environmental Health Key Laboratory of Environment and Health Ministry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical CollegeHuazhong University of Science and Technology Wuhan China.

Background Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2-stage prospective nested case-control design within the Dongfeng-Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case-control pairs using quantitative real-time polymerase chain reaction. We observed that plasma miR-4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07-1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR-4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%-18.83%) increase in plasma miR-4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR-4286 ( coefficients: 0.27 [95% CI, 0.01-0.53] and 0.27 [95% CI, 0.07-0.47] separately by inverse variance-weighted and Mendelian randomization-pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR-4286 explained 5.5% (95% CI, 0.7%-17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR-4286 was associated with an increased risk of ACS. The upregulated miR-4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.
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http://dx.doi.org/10.1161/JAHA.120.018999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174203PMC
March 2021

Chemical Fingerprinting of HULIS in Particulate Matters Emitted from Residential Coal and Biomass Combustion.

Environ Sci Technol 2021 03 3;55(6):3593-3603. Epub 2021 Mar 3.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science and Engineering, Institute of Atmospheric Sciences, Fudan University, Shanghai 200438, China.

Identification of humic-like substances (HULIS) structures and components is still a major challenge owing to their chemical complexity. This study first employed a complementary method with the combination of two-dimensional gas chromatography-time-of-flight mass spectrometry and liquid chromatography-quadrupole-time-of-flight mass spectrometry to address low-polarity and polar components of HULIS in PM (particulate matter with an aerodynamic diameter less than 2.5 μm), respectively. The combination method showed a significant correlation in identifying overlapping species and performed well in uncovering the chemical complexity of HULIS. A total of 1246 compound species in HULIS (65.6-81.0% for each sample), approximately 1 order of magnitude more compounds than that reported in previous studies, were addressed in PM collected in real-world household biomass and coal combustion. Aromatics were the most abundant compounds (37.4-64.1% in biomass and 34.5-70.0% in coal samples) of the total mass in all HULIS samples according to carbon skeleton determination, while the major components included phenols (2.6-21.1%), ketones (6.0-17.1%), aldehydes (1.1-6.8%), esters (2.9-20.0%), amines/amides (3.2-8.5%), alcohols (3.8-17.0%), and acids (4.7-15.1%). Among the identified HULIS species, 11-36% mass in biomass and 11-41% in coal were chromophores, while another 22-35 and 23-29% mass were chromophore precursors, respectively. The combination method shows promise for uncovering HULIS fingerprinting.
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http://dx.doi.org/10.1021/acs.est.0c08518DOI Listing
March 2021

Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome.

Clin Epigenetics 2021 01 27;13(1):19. Epub 2021 Jan 27.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan, 430030, Hubei, China.

Background: Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear.

Methods: We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study.

Results: We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02-1.48; P = 0.03).

Conclusions: We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.
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http://dx.doi.org/10.1186/s13148-021-01004-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839231PMC
January 2021

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
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http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
February 2021

Metabolite Triplet in Serum Improves the Diagnostic Accuracy of Prediabetes and Diabetes Screening.

J Proteome Res 2021 01 21;20(1):1005-1014. Epub 2020 Dec 21.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.

Large-scale population screenings are not feasible by applying laborious oral glucose tolerance tests, but using fasting blood glucose (FPG) and glycated hemoglobin (HbA), a considerable number of diagnoses are missed. A novel marker is urgently needed to improve the diagnostic accuracy of broad-scale diabetes screening in easy-to-collect blood samples. In this study, by applying a novel knowledge-based, multistage discovery and validation strategy, we scaled down from 108 diabetes-associated metabolites to a diagnostic metabolite triplet (Met-T), namely hexose, 2-hydroxybutyric/2-hydroxyisobutyric acid, and phenylalanine. Met-T showed in two independent cohorts, each comprising healthy controls, prediabetic, and diabetic individuals, distinctly higher diagnostic sensitivities for diabetes screening than FPG alone (>79.6 vs <68%). Missed diagnoses decreased from >32% using fasting plasma glucose down to <20.4%. Combining Met-T and fasting plasma glucose further improved the diagnostic accuracy. Additionally, a positive association of Met-T with future diabetes risk was found (odds ratio: 1.41; = 1.03 × 10). The results reveal that missed prediabetes and diabetes diagnoses can be markedly reduced by applying Met-T alone or in combination with FPG and it opens perspectives for higher diagnostic accuracy in broad-scale diabetes-screening approaches using easy to collect sample materials.
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http://dx.doi.org/10.1021/acs.jproteome.0c00786DOI Listing
January 2021

Association of exhaled carbon monoxide with risk of cardio-cerebral-vascular disease in the China Kadoorie Biobank cohort study.

Sci Rep 2020 11 11;10(1):19507. Epub 2020 Nov 11.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hongkong Rd, Wuhan, 430030, Hubei, People's Republic of China.

Exhaled carbon monoxide (COex) level has been proposed as a noninvasive and easily-obtainable cardiovascular risk marker, however, with limited prospective evidence, and its association with stroke risk has been rarely explored. Measurements of COex were performed during 2004-2008 baseline examinations in the China Kadoorie Biobank study among 512,891 adults aged 30-79 years from 10 diverse study areas. After excluding participants with baseline cardiopulmonary diseases, stroke and cancer, 178,485 men and 267,202 women remained. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of cardio-cerebral-vascular disease (CCVD) associated with COex levels, with sequential addition of adjustment for proxy variables for CO exposure, including study area indexing ambient CO variations at large, and smoking and solid fuel use, apart from adjusting for traditional cardiovascular risk factors. During 7-year follow-up, we documented 1744 and 1430 major coronary events (myocardial infarction plus fatal ischemic heart disease), 8849 and 10,922 ischemic strokes, and 2492 and 2363 hemorrhagic strokes among men and women, respectively. The HRs with 95% CIs comparing the highest with lowest COex quintile were 2.15 [1.72, 2.69] for major coronary events, 1.65 [1.50, 1.80] for ischemic stroke, and 1.35 [1.13, 1.61] for hemorrhagic stroke among men, while among women higher associated risk was only observed for major coronary events (1.64 [1.35, 2.00]) and ischemic stroke (1.87 [1.73, 2.01]). The elevated risks were consistent when COex level was over 3 ppm. However, these associations were all attenuated until null by sequential addition of stratification by study areas, and adjustments of smoking and solid fuel use. Nevertheless, the association with ischemic stroke was maintained among the subgroup of male smokers even with adjustment for the depth and amount of cigarette smoking (HR [95% CI]: 1.37 [1.06, 1.77]), while a negative association with hemorrhagic stroke also appeared within this subgroup. Higher COex level (over 3 ppm) was associated with elevated risk of ischemic CCVD, but not independently of CO exposure. Our finding suggests that, though not an independent risk factor, COex could potentially provide a cost-effective biomarker for ischemic cardio-cerebral-vascular risk, given that CO exposure is ubiquitous.
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http://dx.doi.org/10.1038/s41598-020-76353-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659340PMC
November 2020

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges.

Authors:
Tangchun Wu

Front Med 2020 12 24;14(6):816-819. Epub 2020 Oct 24.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

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http://dx.doi.org/10.1007/s11684-020-0823-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585350PMC
December 2020

Association between urinary metals levels and metabolic phenotypes in overweight and obese individuals.

Chemosphere 2020 Sep 19;254:126763. Epub 2020 Apr 19.

Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Epidemiologic studies suggest that circulating metals from the natural environment are linked with cardiometabolic health. However, few studies examined the relationship between multiple metals exposure and metabolic phenotypes, especially in obese individuals. We conducted a cross-sectional study to explore the association between 23 urinary metals and metabolic phenotypes in 1392 overweight and obese individuals (592 males, 800 females, mean age 43.1 ± 9.8 years). Participants were classified as metabolically unhealthy if they had ≥2 of the following metabolic abnormalities: elevated blood pressure, elevated fasting blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol. Odds ratios (ORs) of unhealthy metabolic phenotypes for metal levels categorized into tertiles were assessed using logistic regression models. Five metals (barium, copper, iron, uranium, and zinc) were associated with unhealthy metabolic phenotypes in single-metal models, while in the multiple-metal model, only zinc and zinc-copper ratio remained significant. The ORs (95% CIs) comparing extreme tertiles were 2.57 (1.69, 3.89) for zinc and 1.68 (1.24, 2.27) for zinc-copper ratio after adjustment for confounders (both p-trends were <0.001). The numbers of metabolic abnormalities significantly increased with the levels of zinc and the zinc-copper ratio increased. Similar associations were observed with metabolic syndrome risk. High levels of urinary zinc were positively associated with elevated fasting blood glucose (p-trend < 0.001) and elevated triglycerides (p-trend = 0.003). The results suggest that urinary zinc and zinc-copper ratio are positively associated with increased risk of unhealthy metabolic phenotype. Further prospective studies with a larger sample size are required to verify these findings.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126763DOI Listing
September 2020

Corrigendum to "Circulating essential metals and lung cancer: Risk assessment and potential molecular effects" [Environ. Int. 127 (2019) 685-693].

Environ Int 2020 Oct 1;143:106072. Epub 2020 Sep 1.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2020.106072DOI Listing
October 2020

Association between weight status, metabolic syndrome, and chronic kidney disease among middle-aged and elderly Chinese.

Nutr Metab Cardiovasc Dis 2020 10 1;30(11):2017-2026. Epub 2020 Jul 1.

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR China. Electronic address:

Background And Aims: Obesity often initiates or coexists with certain metabolic abnormalities. This study sought to examine the independent and joint relations of weight and metabolic syndrome (MetS) with incident chronic kidney disease (CKD) among Chinese elderly people.

Methods And Results: A total of 15,229 participants (mean age: 62.8 years) from the Dongfeng-Tongji cohort with complete baseline questionnaire and medical examination data were followed from 2008 to 2010 to 2013. All participants were categorized into four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically unhealthy overweight/obesity (MUO). Multivariable-adjusted logistic regression models were applied to estimate the odds ratios (ORs) and confidence intervals (CIs) of four phenotypes with the risk of incident CKD, which was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m. A total of 1151 CKD cases were identified during a mean of 4.6-year follow-up. After adjusting for potential confounders, both overweight/obesity and MetS were associated with higher risk of CKD, and the ORs (95% CI) were 1.32 (1.15-1.52) and 1.50 (1.31-1.73), respectively. The risk of CKD was progressively higher in MHO (1.31, 1.09-1.57), MUNO (1.54, 1.22-1.93), and MUO (2.05, 1.73-2.42) as compared with MHNO phenotype, without significant multiplicative interaction between overweight/obesity and MetS (P = 0.906). These associations were slightly stronger among those aged >60 years or with baseline diabetes.

Conclusion: Both overweight/obesity and MetS were associated with an increased risk of CKD. It is worth noting that MHO and MUNO also have an elevated risk. Maintaining both normal weight and healthy metabolic profile is recommended.
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http://dx.doi.org/10.1016/j.numecd.2020.06.025DOI Listing
October 2020

Clinical Characteristics and Prognosis of 244 Cardiovascular Patients Suffering From Coronavirus Disease in Wuhan, China.

J Am Heart Assoc 2020 10 14;9(19):e016796. Epub 2020 Aug 14.

Department of Cardiology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China.

Background The coronavirus disease 2019 (COVID-19) has developed into a global outbreak. Patients with cardiovascular disease (CVD) with COVID-19 have different clinical characteristics and prognostic outcomes. This study aimed to summarize the clinical characteristics and laboratory indicators of patients with COVID-19 with CVD, especially the critically ill patients. Methods and Results This study included 244 patients diagnosed with COVID-19 and CVD (hypertension, coronary heart disease, or heart failure). The patients were categorized into critical (n=36) and noncritical (n=208) groups according to the interim guidance of China's National Health Commission. Clinical, laboratory, and outcome data were collected from the patients' medical records and compared between the 2 groups. The average body mass index of patients was significantly higher in the critical group than in the noncritical group. Neutrophil/lymphocyte ratio, and C-reactive protein, procalcitonin, and fibrinogen, and d-dimer levels at admission were significantly increased in the critical group. The all-cause mortality rate among cases of COVID-19 combined with CVD was 19.26%; the proportion of coronary heart disease and heart failure was significantly higher in deceased patients than in recovered patients. High body mass index, previous history of coronary heart disease, lactic acid accumulation, and a decrease in the partial pressure of oxygen were associated with death. Conclusions All-cause mortality in patients with COVID-19 with CVD in hospitals is high. The high neutrophil/lymphocyte ratio may be a predictor of critical patients. Overweight/obesity combined with coronary heart disease, severe hypoxia, and lactic acid accumulation resulting from respiratory failure are related to poor outcomes. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000029865.
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http://dx.doi.org/10.1161/JAHA.120.016796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792394PMC
October 2020

Serum piRNA-54265 is a New Biomarker for early detection and clinical surveillance of Human Colorectal Cancer.

Theranostics 2020 9;10(19):8468-8478. Epub 2020 Jul 9.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Our previous study has demonstrated an oncogenic role of PIWI-interacting RNA-54265 (piR-54265) in colorectal cancer (CRC). Here, we investigate whether it can be a blood biomarker for population screening and clinical applications. Serum piR-54265 levels were determined by a digital PCR method in 209 cancer-free healthy controls, 725 patients with CRC, 1303 patients with other types of digestive cancer and 192 patients with benign colorectal tumors. A prospective case-control analysis was conducted to assess the predictive value of serum piR-54265 for future CRC diagnosis. Receiver operating characteristic (ROC) curve was constructed to quantify the diagnostic performance of serum piR-54265 levels by assessing its sensitivity, specificity and respective areas under curve (AUC). The odds ratios (ORs) were computed using multivariate logistic regression models. Serum piR-54265 levels were significantly elevated only in patients with CRC compared with controls and patients with other cancer types. The AUC for recognizing CRC was 0.896 (95% CI, 0.874-0.914), with a sensitivity and specificity being 85.7% and 65.1% at 1500 copies/µL as a cut-off value. The serum piR-54265 levels in patients declined substantially after surgery but increased significantly again when tumor relapses. The prediagnostic serum piR-54265 levels were significantly associated with future CRC diagnosis, with the ORs of 7.23, 2.80, 2.45, and 1.24 for those whose CRC was diagnosed within 1, 2, 3 and >3 years. Serum piR-54265 test is more sensitive than other blood CRC markers. Serum piR-54265 may serve as a valuable biomarker for CRC screening, early detection and clinical surveillance.
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http://dx.doi.org/10.7150/thno.46241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392023PMC
May 2021

Cost-Effectiveness of Drug Treatment for Chinese Patients With Stage I Hypertension According to the 2017 Hypertension Clinical Practice Guidelines.

Hypertension 2020 09 27;76(3):750-758. Epub 2020 Jul 27.

From the Department of Epidemiology and Biostatistics (Y.-F.Z., N.L., X.-Y.S., X.-F.P., A.P.), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Systolic/diastolic blood pressure of 130 to 139/80 to 89 mm Hg has been defined as stage I hypertension by the 2017 Hypertension Clinical Practice Guidelines. Drug treatment is recommended for stage I hypertensive patients aged ≥65 years without cardiovascular disease in the 2017 Hypertension Clinical Practice Guidelines but not in the 2018 Chinese guidelines. However, the cost-effectiveness of drug treatment among this subgroup of Chinese patients is unclear. This study developed a microsimulation model to compare costs and effectiveness of drug treatment and nondrug treatment for the subgroup of stage I hypertensive patients over a lifetime horizon from a government affordability perspective. Event rates of mortality and cardiovascular complications were estimated from 3 cohorts in the Chinese population. Costs and health utilities were obtained from the national statistics report and published literature. The model predicted that drug treatment generated quality-adjusted life-years of 13.52 and associated with expected costs of $6825 in comparison with 13.81 and $7328 produced by nondrug treatment over a lifetime horizon among stage I hypertensive patients aged ≥65 years without cardiovascular disease. At a willingness-to-pay threshold of $8836/quality-adjusted life-year (the GDP per capita in 2017), drug treatment only had a 1.8% probability of being cost-effective compared with nondrug treatment after 10 000 probabilistic simulations. Sensitivity analysis of treatment costs, benefits expected from treatment, health utilities, and discount rates did not change the results. Our results suggested that drug treatment was not cost-effective compared with nondrug treatment for stage I hypertensive patients aged ≥65 years without cardiovascular disease in China.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429361PMC
September 2020

Helicobacter pylori infection and the prevalence of hypertension in Chinese adults: The Dongfeng-Tongji cohort.

J Clin Hypertens (Greenwich) 2020 08 20;22(8):1389-1395. Epub 2020 Jul 20.

Hubei University of Medicine Affiliated Dongfeng Hospital, Hubei, China.

Although many studies explored the association between helicobacter pylori (H pylori) infection and hypertension, there is no consensus. This study is to investigate the association between H pylori infection and the prevalence of hypertension among a middle- and old-age Chinese population. A cross-sectional study including 17,100 participants from the Dongfeng-Tongji cohort study was performed. All participants underwent a C-urea breath test and a routine health check-up. Logistics and linear regression with multivariable adjustment were used to quest the association between H pylori infection and hypertension. The individuals with H pylori infection had a higher prevalence of hypertension (57.5% vs 55.1%, P = .002), and infection rate of H pylori in patients with hypertension is higher than that in non-hypertensive individuals (48.8% vs 46.4%, P = .002). After adjustment for potential confounders, H pylori infection increased the prevalence of hypertension (odds ratio, 1.117, 95% confidence interval (CI), 1.029-1.213, P = .008). Moreover, compared with participants without H pylori infection, individuals infected had an increase of 0.905 mm Hg (95% CI, 0.025-1.785, P = .044) for diastolic blood pressure. However, there was no interaction between H pylori infection and traditional risk factors on hypertension. These findings suggested that H pylori infection was positively associated with the prevalence of hypertension.
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http://dx.doi.org/10.1111/jch.13928DOI Listing
August 2020

Healthy lifestyle and cancer risk among Chinese population in the Dongfeng-Tongji cohort.

Ann Med 2020 11 30;52(7):393-402. Epub 2020 Jul 30.

Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Studies on the association between healthy lifestyle and cancer risk are limited among the old Chinese population.

Methods: The healthy lifestyle score was derived from smoking, drinking, diet, body mass index and physical activity among 23734 retired employees from the Dongfeng-Tongji Cohort. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). The rate advancement periods (RAPs) and the population attributable risk percentage (PAR%) were estimated to indicate the benefits of removing risk lifestyle factors.

Results: During a median follow-up of 8.16 years, 2023 cancer cases were identified. Compared with 0-2 points of the healthy lifestyle score, the HRs were 0.87 (95% CI: 0.76, 0.99), 0.83 (95% CI: 0.73, 0.94), and 0.74 (95% CI: 0.64, 0.86) for 3, 4, and 5 points, respectively, with the corresponding RAPs of -4.40 (95% CI: -8.39, -0.41), -5.84 (95% CI: -9.77, -1.90), and -9.14 (95% CI: -14.03, -4.25), respectively. Approximately 15% of incident cancer cases among total population and 22% among men would be prevented by following all 5 healthy lifestyle factors.

Conclusions: The current study suggests that healthy lifestyle could reduce cancer risk in the retired Chinese population, especially in males. Key messages Healthy lifestyle derived by smoking, drinking, diet, body mass index and physical activity presented a strong protective effect on cancer risk among the retired Chinese population, especially in males. We employed the rate advancement periods and the population attributable risk percentage to indicate the benefits of adopting healthy lifestyle and we found that following all 5 healthy lifestyle factors could delay the risk of developing cancer by 9.14 years and prevent 15% of incident cancer cases.
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http://dx.doi.org/10.1080/07853890.2020.1798017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877923PMC
November 2020

Reconstruction of the full transmission dynamics of COVID-19 in Wuhan.

Nature 2020 08 16;584(7821):420-424. Epub 2020 Jul 16.

Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

As countries in the world review interventions for containing the pandemic of coronavirus disease 2019 (COVID-19), important lessons can be drawn from the study of the full transmission dynamics of its causative agent-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- in Wuhan (China), where vigorous non-pharmaceutical interventions have suppressed the local outbreak of this disease. Here we use a modelling approach to reconstruct the full-spectrum dynamics of COVID-19 in Wuhan between 1 January and 8 March 2020 across 5 periods defined by events and interventions, on the basis of 32,583 laboratory-confirmed cases. Accounting for presymptomatic infectiousness, time-varying ascertainment rates, transmission rates and population movements, we identify two key features of the outbreak: high covertness and high transmissibility. We estimate 87% (lower bound, 53%) of the infections before 8 March 2020 were unascertained (potentially including asymptomatic and mildly symptomatic individuals); and a basic reproduction number (R) of 3.54 (95% credible interval 3.40-3.67) in the early outbreak, much higher than that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We observe that multipronged interventions had considerable positive effects on controlling the outbreak, decreasing the reproduction number to 0.28 (95% credible interval 0.23-0.33) and-by projection-reducing the total infections in Wuhan by 96.0% as of 8 March 2020. We also explore the probability of resurgence following the lifting of all interventions after 14 consecutive days of no ascertained infections; we estimate this probability at 0.32 and 0.06 on the basis of models with 87% and 53% unascertained cases, respectively-highlighting the risk posed by substantial covert infections when changing control measures. These results have important implications when considering strategies of continuing surveillance and interventions to eventually contain outbreaks of COVID-19.
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http://dx.doi.org/10.1038/s41586-020-2554-8DOI Listing
August 2020

Wuhan COVID-19 data - An example to show the importance of public health interventions to fight against the pandemic.

Authors:
An Pan Tangchun Wu

Toxicology 2020 08 12;441:152523. Epub 2020 Jun 12.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.tox.2020.152523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291978PMC
August 2020

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

Eur J Epidemiol 2020 Jul 7;35(7):685-697. Epub 2020 May 7.

Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, 21741, Malmö, Sweden.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (β = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.
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http://dx.doi.org/10.1007/s10654-020-00638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867117PMC
July 2020

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Mol Psychiatry 2020 May 5. Epub 2020 May 5.

Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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http://dx.doi.org/10.1038/s41380-020-0719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641978PMC
May 2020

Association of blood lipid profile with incident chronic kidney disease: A Mendelian randomization study.

Atherosclerosis 2020 05 27;300:19-25. Epub 2020 Mar 27.

Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hongkong Rd, Wuhan, 430030, Hubei, China. Electronic address:

Background And Aims: Cohort studies found blood lipid traits were associated with the risk of chronic kidney disease (CKD). We aimed to investigate whether blood lipid traits were causally associated with the risk of CKD in the Chinese.

Methods: 15,244 participants without kidney disease and cancer from the Dongfeng-Tongji cohort were recruited in 2008-2010 in Shiyan City, China. Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were measured. 5251 participants had genotype data and were included in the Mendelian randomization analysis. Incident CKD was defined as estimated glomerular filtration rate <60 ml/min per 1.73 m in 2013. Logistic regression and Mendelian randomization methods were used to estimate the observed and causal associations of blood lipid traits with incident CKD.

Results: Various blood lipid traits were associated with CKD risk, and the odds ratios (95% confidence intervals) for incident CKD comparing the extreme quartiles were 1.45 (1.24-1.70) for TG, 1.26 (1.08-1.46) for nonHDL-c, 2.21 (1.91-2.57) for TC:HDL-c ratio, 2.14 (1.83-2.51) for TG:HDL-c ratio, and 0.47 (0.40-0.55) for HDL-c. The Mendelian randomization analysis indicated that 1 mmol/l increase in the genetic predicted blood TG level was associated with a 5% (95% confidence interval, 0-10%) higher risk of CKD.

Conclusions: Although blood levels of HDL-c, TG, nonHDL-c, TC:HDL-c ratio, and TG:HDL-c ratio were observed to be associated with incident CKD, the Mendelian randomization analysis provided genetic evidence to support causal relation for blood TG level only.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.03.020DOI Listing
May 2020

Association of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China.

JAMA 2020 May;323(19):1915-1923

Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Importance: Coronavirus disease 2019 (COVID-19) has become a pandemic, and it is unknown whether a combination of public health interventions can improve control of the outbreak.

Objective: To evaluate the association of public health interventions with the epidemiological features of the COVID-19 outbreak in Wuhan by 5 periods according to key events and interventions.

Design, Setting, And Participants: In this cohort study, individual-level data on 32 583 laboratory-confirmed COVID-19 cases reported between December 8, 2019, and March 8, 2020, were extracted from the municipal Notifiable Disease Report System, including patients' age, sex, residential location, occupation, and severity classification.

Exposures: Nonpharmaceutical public health interventions including cordons sanitaire, traffic restriction, social distancing, home confinement, centralized quarantine, and universal symptom survey.

Main Outcomes And Measures: Rates of laboratory-confirmed COVID-19 infections (defined as the number of cases per day per million people), across age, sex, and geographic locations were calculated across 5 periods: December 8 to January 9 (no intervention), January 10 to 22 (massive human movement due to the Chinese New Year holiday), January 23 to February 1 (cordons sanitaire, traffic restriction and home quarantine), February 2 to 16 (centralized quarantine and treatment), and February 17 to March 8 (universal symptom survey). The effective reproduction number of SARS-CoV-2 (an indicator of secondary transmission) was also calculated over the periods.

Results: Among 32 583 laboratory-confirmed COVID-19 cases, the median patient age was 56.7 years (range, 0-103; interquartile range, 43.4-66.8) and 16 817 (51.6%) were women. The daily confirmed case rate peaked in the third period and declined afterward across geographic regions and sex and age groups, except for children and adolescents, whose rate of confirmed cases continued to increase. The daily confirmed case rate over the whole period in local health care workers (130.5 per million people [95% CI, 123.9-137.2]) was higher than that in the general population (41.5 per million people [95% CI, 41.0-41.9]). The proportion of severe and critical cases decreased from 53.1% to 10.3% over the 5 periods. The severity risk increased with age: compared with those aged 20 to 39 years (proportion of severe and critical cases, 12.1%), elderly people (≥80 years) had a higher risk of having severe or critical disease (proportion, 41.3%; risk ratio, 3.61 [95% CI, 3.31-3.95]) while younger people (<20 years) had a lower risk (proportion, 4.1%; risk ratio, 0.47 [95% CI, 0.31-0.70]). The effective reproduction number fluctuated above 3.0 before January 26, decreased to below 1.0 after February 6, and decreased further to less than 0.3 after March 1.

Conclusions And Relevance: A series of multifaceted public health interventions was temporally associated with improved control of the COVID-19 outbreak in Wuhan, China. These findings may inform public health policy in other countries and regions.
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http://dx.doi.org/10.1001/jama.2020.6130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149375PMC
May 2020