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.

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.

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.

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.

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.

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.

Objective:To explore the relationship between glycosylated hemoglobin A 1c/high-density lipoprotein cholesterol ratio (HbA 1c/HDL-C) and urinary albumin-creatinine ratio (UACR) in Chinese adults. Methods:In this cross-sectional study, the clinical data of 43 820 community residents (age>40 years) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals (REACTION study; March-December 2012) across eight centers (Liaoning, Guangdong, Shanghai, Gansu, Guangxi, Henan, Hubei, and Sichuan) in China were collected and analyzed. Participants were divided into three groups based on UACR levels:<10 mg/g, 10-30 mg/g, and >30 mg/g. The HbA 1c/HDL-C ratio was divided into four groups according to quartile division of the subjects: 1st quartile (Q1<3.79), 2nd quartile (3.79≤Q2<4.59), 3rd quartile (4.59≤Q3≤5.66), and 4th quartile (Q4>5.66). Multivariate ordinal logistic regression model was used to analyze the relationship between HbA 1c/HDL-C and UACR. Receiver operating characteristic (ROC) analysis was used to explore the predictive value of HbA 1c/HDL-C to UACR. Results:The 43 820 subjects included 13 452 (30.70%) male and 30 378 (69.30%) female patients, with an average age of (58.00±0.05) years. According to results of one-way analysis of variance analysis, the HbA 1c/HDL-C ratio was significantly associated with the risk of increased UACR ( F=495.73, P<0.001). After adjusting for clinically relevant confounding variables in logistic regression model, compared with participants with the lowest HbA 1c/HDL-C ratio (Q1), women with the highest HbA 1c/HDL-C ratio (Q4) had a 1.483-fold (95% CI 1.376-1.598, P<0.001) and men had a 1.161-fold (95% CI 1.019-1.323, P<0.001) increased risk of UACR. The ROC curve analysis showed that the area under the curve of HbA 1c/HDL-C for predicting increased UACR was 0.623 (95% CI 0.597-0.606), with a sensitivity of 60.18% and a specificity of 54.91%. The HbA 1c/HDL-C ratio showed the highest predictive value of all glycemic and lipidemic parameters. In individuals with well-controlled blood glucose (HbA 1c<6.5%) or lipid levels (HDL-C≥1.0 mmol/L), the HbA 1c/HDL-C ratio was still independently associated with the risk of increased UACR after adjusting for confounding variables [ OR(95% CI) of quartile 4: 1.563 (1.210-2.019, P=0.001) in participants with HbA 1c<6.5% and 1.822 (1.687-1.968, P<0.001) in participants with HDL-C≥1.0 mmol/L]. Conclusion:As a novel compound indicator for evaluating glucose homeostasis and dyslipidemia, the HbA 1c/HDL-C ratio was independently associated with increased UACR in the general population aged>40 years in China, which was superior to both glycemic and lipid parameters alone.

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.

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.