1.Association between DNA methylation clock and obesity-related indicators:A longi-tudinal twin study
Shunkai LIU ; Weihua CAO ; Jun LV ; Canqing YU ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Runhua HU ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Yu LIU ; Wenjing GAO ; Liming LI
Journal of Peking University(Health Sciences) 2025;57(3):456-464
Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0%,males for 68.0%,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5%,males for 60.8%,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95%CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95%CI:-0.05 to-0.01;β=-0.07,95%CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95%CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.
2.Distribution characteristics of smoking behavior among adult twins in China
Shunkai LIU ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Jianrui WANG ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Preventive Medicine 2025;59(7):1090-1096
This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.
3.Distribution characteristics and heritability of alcohol consumption behavior in adult twins in China
Yuanchen LI ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Yanxia MA ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Epidemiology 2025;46(1):73-80
Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.
5.Distribution characteristics of smoking behavior among adult twins in China
Shunkai LIU ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Jianrui WANG ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Preventive Medicine 2025;59(7):1090-1096
This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.
6.Association between DNA methylation clock and obesity-related indicators:A longi-tudinal twin study
Shunkai LIU ; Weihua CAO ; Jun LV ; Canqing YU ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Runhua HU ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Yu LIU ; Wenjing GAO ; Liming LI
Journal of Peking University(Health Sciences) 2025;57(3):456-464
Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0%,males for 68.0%,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5%,males for 60.8%,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95%CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95%CI:-0.05 to-0.01;β=-0.07,95%CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95%CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.
7.Distribution characteristics and heritability of alcohol consumption behavior in adult twins in China
Yuanchen LI ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Yanxia MA ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Epidemiology 2025;46(1):73-80
Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.
8.Predictive value of MRI imaging examination in secondary dementia of cognitive impairment of patients with Parkinson disease
Ting SUN ; Jianbing ZHU ; Qing MA ; Hongquan PANG ; Wenjing XU
China Medical Equipment 2024;21(12):83-87
Objective:To analyze the predictive value of magnetic resonance imaging (MRI) examination in secondary dementia of cognitive impairment of patients with Parkinson disease (PD). Methods:A total of 100 PD patients with cognitive dysfunction,who admitted to the Affiliated Suzhou Hospital of Nanjing University Medical School and the Second Affiliated Hospital of Soochow University,were selected. They were divided into observation group (30 cases) and control group (70 cases) according to the Hasegawa Dementia Scale (HDS) score. The HDS score of observation group was ≤ 21.5 points,which had occurred secondary dementia,while the HDS score of control group was>21.5 points,which had not occurred secondary dementia. The imaging parameters,which included apparent diffusion coefficient (ADC) and fractional anisotropy (FA) index of magnetic resonance imaging (MRI),between two groups were compared. Logistic regression analysis was used to identify the risk factors for secondary dementia of PD patients with cognitive impairment. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of MRI imaging parameters for the secondary dementia of PD patients with cognitive impairment. Results:Compared with substantia nigra of the control group,the observation group had higher ADC values and lower FA values in substantia nigra,and the differences of them between the two groups were statistically significant (t=2.837,4.581,P<0.05),respectively. The ADC value and FA value of substantia nigra,age,PD duration and homocysteine (Hcy) were risk factors for the secondary dementia of cognitive impairment of PD patients (OR=1.537,1.346,1.134,1.351,1.625,P<0.05),respectively. The area under curve (AUC) value,sensitivity,specificity of the combined detection of ADC value and FA value of substantia nigra were respectively 0.861,94.86% and 82.18% in predict the secondary dementia of cognitive impairment of PD patients,and the predictive efficiency of combined detection was higher (95%CI:0.812-0.960,P<0.05). Conclusion:The increase of ADC value and the decrease of FA value of substantia nigra closely relate to the secondary dementia of cognitive dysfunction of PD patients. The combined detection of ADC value and FA value of substantia nigra can improve predictive efficiency of dementia.
9.Diagnostic predictive value of preoperative hematological inflammatory markers in differentiating malignant and benign primary retroperitoneal tumors
Wenyang PANG ; Wenjing CHEN ; Jinji JIN ; Wenyi WU ; Pengfei WANG ; Guanbao ZHU ; Xiaolei CHEN ; Yiqi CAI
Chinese Journal of Endocrine Surgery 2024;18(6):865-869
Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.
10.Exploration on the Medication Law of Zhang Binghou in Treating Diabetic Kidney Disease Based on Data Mining
Mengyu LI ; Haitao SHANG ; Shiwen ZHANG ; Wenjing ZHAO ; Zhen CAI ; Xinxin PANG ; Xiaodan YIN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):58-65
Objective To analyze Professor Zhang Binghou's medication experience in the treatment of diabetic kidney disease using data mining methods;To screen the core medicinal pairs and medicinal groups.Methods Prescriptions of diabetic kidney disease of Professor Zhang Binghou from the outpatient department of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were selected from January 2014 to December 2021.TCM Inheritance Platform System 2.5,SPSS Modeler 18 and SPSS Statistics 21 software were used for association rules,clustering analysis and factor analysis to summarize the medication frequency,properties and tastes and meridians,and medicinal pairs and combinations.Results A total of 161 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 2 220 time.The kinds of Chinese materia medica with higher frequency were Rehmannize Radix et Praeparata,Testudinis Carapax et Plastrum,Astragali Radix,Rehmannine Radix,etc.The main properties were cold and warm,the main tastes were sweet and bitter,and the main meridians were kidney,liver and spleen meridians.A total of 14 drug pair association rules were obtained,with 27 commonly used drug combinations.Clustering analysis extracted 10 combinations based on the spectrum,and factor analysis extracted 14 common factors.Conclusion Professor Zhang Binghou's treatment for diabetic kidney disease takes nourishing the true yin and clearing away damp-heat as the main treatment method,and at the same time,it pays attention to tonifying kidney,consolidating essence,nourishing yin and containing yang,promoting blood circulation and removing blood stasis,etc.,which embodies Professor Zhang Binghou's unique academic thought of treating diabetic kidney disease.

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