Five years of change in adult twins: longitudinal changes of genetic and environmental influence on epigenetic clocks.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Association of psychological distress and DNA methylation: A 5-year longitudinal population-based twin study.

AIM: To identify the psychological distress (PD)-associated 5'-cytosine-phosphate-guanine-3' sites (CpGs), and investigate the temporal relationship between dynamic changes in DNA methylation (DNAm) and PD. METHODS: This study included 1084 twins from the Chinese National Twin Register (CNTR). The CNTR conducted epidemiological investigations and blood withdrawal twice in 2013 and 2018. These included twins were used to perform epigenome-wide association studies (EWASs) and to validate the previously reported PD-associated CpGs selected from previous EWASs in PubMed, Embase, and the EWAS catalog. Next, a cross-lagged study was performed to examine the temporality between changes in DNAm and PD in 308 twins who completed both 2013 and 2018 surveys. RESULTS: The EWAS analysis of our study identified 25 CpGs. In the validation analysis, 741 CpGs from 29 previous EWASs on PD were selected for validation, and 101 CpGs were validated to be significant at a false discovery rate <0.05. The cross-lagged analysis found a unidirectional path from PD to DNAm at 14 CpGs, while no sites showed significance from DNAm to PD. CONCLUSIONS: This study identified and validated PD-related CpGs in a Chinese twin population, and suggested that PD may be the cause of changes in DNAm over time. The findings provide new insights into the molecular mechanisms underlying PD pathophysiology.

Genetic and Environmental Influences on Blood Pressure and Serum Lipids Across Age-Groups.

Aging plays a crucial role in the mechanisms of the impacts of genetic and environmental factors on blood pressure and serum lipids. However, to our knowledge, how the influence of genetic and environmental factors on the correlation between blood pressure and serum lipids changes with age remains to be determined. In this study, data from the Chinese National Twin Registry (CNTR) were used. Resting blood pressure, including systolic and diastolic blood pressure (SBP and DBP), and fasting serum lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) were measured in 2378 participants (1189 twin pairs). Univariate and bivariate structural equation models examined the genetic and environmental influences on blood pressure and serum lipids among three age groups. All phenotypes showed moderate to high heritability (0.37-0.59) and moderate unique environmental variance (0.30-0.44). The heritability of all phenotypes showed a decreasing trend with age. Among all phenotypes, SBP and DBP showed a significant monotonic decreasing trend. For phenotype-phenotype pairs, the phenotypic correlation (Rph) of each pair ranged from -0.04 to 0.23, and the additive genetic correlation (Ra) ranged from 0.00 to 0.36. For TC&SBP, TC&DBP, TG&SBP and TGs&DBP, both the Rph and Ra declined with age, and the Ra difference between the young group and the older adult group is statistically significant (p < .05). The unique environmental correlation (Re) of each pair did not follow any pattern with age and remained relatively stable with age. In summary, we observed that the heritability of blood pressure was affected by age. Moreover, blood pressure and serum lipids shared common genetic backgrounds, and age had an impact on the phenotypic correlation and genetic correlations.

Exploring the Genetic Association between Obesity and Serum Lipid Levels Using Bivariate Methods.

It is crucial to understand the genetic mechanisms and biological pathways underlying the relationship between obesity and serum lipid levels. Structural equation models (SEMs) were constructed to calculate heritability for body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the genetic connections between BMI and the four classes of lipids using 1197 pairs of twins from the Chinese National Twin Registry (CNTR). Bivariate genomewide association studies (GWAS) were performed to identify genetic variants associated with BMI and lipids using the records of 457 individuals, and the results were further validated in 289 individuals. The genetic background affecting BMI may differ by gender, and the heritability of males and females was 71% (95% CI [.66, .75]) and 39% (95% CI [.15, .71]) respectively. BMI was positively correlated with TC, TG and LDL-C in phenotypic and genetic correlation, while negatively correlated with HDL-C. There were gender differences in the correlation between BMI and lipids. Bivariate GWAS analysis and validation stage found 7 genes (LOC105378740, LINC02506, CSMD1, MELK, FAM81A, ERAL1 and MIR144) that were possibly related to BMI and lipid levels. The significant biological pathways were the regulation of cholesterol reverse transport and the regulation of high-density lipoprotein particle clearance (p < .001). BMI and blood lipid levels were affected by genetic factors, and they were genetically correlated. There might be gender differences in their genetic correlation. Bivariate GWAS analysis found MIR144 gene and its related biological pathways may influence obesity and lipid levels.

Blood DNA methylation markers associated with type 2 diabetes, fasting glucose, and HbA1c levels: An epigenome-wide association study in 316 adult twin pairs.

DNA methylation plays an important role in the development and etiology of type 2 diabetes; however, few epigenomic studies have been conducted on twins. Herein, a two-stage study was performed to explore the associations between DNA methylation and type 2 diabetes, fasting plasma glucose, and HbA1c. DNA methylation in 316 twin pairs from the Chinese National Twin Registry (CNTR) was measured using Illumina Infinium BeadChips. In the discovery sample, the results revealed that 63 CpG sites and 6 CpG sites were significantly associated with fasting plasma glucose and HbA1c, respectively. In the replication sample, cg19690313 in TXNIP was associated with both fasting plasma glucose (P = 1.23 × 10-17, FDR < 0.001) and HbA1c (P = 2.29 × 10-18, FDR < 0.001). Furthermore, cg04816311, cg08309687, and cg09249494 may provide new insight in the metabolic mechanism of HbA1c. Our study provides solid evidence that cg19690313 on TXNIP correlates with HbA1c and fasting plasma glucose levels.

Associations of Obesity Measurements with Serum Metabolomic Profile: A Chinese Twin Study.

The objective of this study was to investigate how different obesity measures link to circulating metabolites, and whether the connections are due to genetic or environmental factors. A cross-sectional analysis was performed on follow-up survey data at the Chinese National Twin Registry (CNTR), which was conducted in four areas of China (Shandong, Jiangsu, Zhejiang and Sichuan) in 2013. The survey collected detailed questionnaire information and conducted physical examinations, fasting blood sampling and untargeted metabolomic measurements among 439 adult twins. Linear regression models and bioinformatics analysis were used to examine the relation of obesity measures, including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with serum metabolite levels and related pathways. A co-twin control study was additionally conducted among 15 obesity-discordant monozygotic (MZ) pairs (intrapair BMI difference >3 kg/m2) to examine any differences in metabolites controlling for genetic factors. Eleven metabolites were associated with BMI, WC and WHR after controlling for genetic and shared environmental factors. Pathway analysis identified pathways such as phenylalanine metabolism, purine metabolism, valine, leucine and isoleucine biosynthesis that were associated with obesity. A wide range of unfavorable alterations in the serum metabolome was associated with obesity. Obesity-discordant twin analysis suggests that these associations are independent of genetic liability.

A Comparison of Preterm Birth Rate and Growth from Birth to 18 Years Old between in Vitro Fertilization and Spontaneous Conception of Twins.

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.

The Chinese National Twin Registry: A Unique Data Source for Systems Epidemiology of Complex Disease.

The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.

Genome-scale MicroRNA target prediction through clustering with Dirichlet process mixture model.

BACKGROUND: MicroRNA regulation is fundamentally responsible for fine-tuning the whole gene network in human and has been implicated in most physiological and pathological conditions. Studying regulatory impact of microRNA on various cellular and disease processes has resulted in numerous computational tools that investigate microRNA-mRNA interactions through the prediction of static binding site highly dependent on sequence pairing. However, what hindered the practical use of such target prediction is the interplay between competing and cooperative microRNA binding that complicates the whole regulatory process exceptionally. RESULTS: We developed a new method for improved microRNA target prediction based on Dirichlet Process Gaussian Mixture Model (DPGMM) using a large collection of molecular features associated with microRNA, mRNA, and the interaction sites. Multiple validations based on microRNA-mRNA interactions reported in recent large-scale sequencing analyses and a screening test on the entire human transcriptome show that our model outperformed several state-of-the-art tools in terms of promising predictive power on binding sites specific to transcript isoforms with reduced false positive prediction. Last, we illustrated the use of predicted targets in constructing conditional microRNA-mediated gene regulation networks in human cancer. CONCLUSION: The probability-based binding site prediction provides not only a useful tool for differentiating microRNA targets according to the estimated binding potential but also a capability highly important for exploring dynamic regulation where binding competition is involved.

Association of Educational Level and Marital Status With Obesity: A Study of Chinese Twins.

The prevalence of overweight and obesity is growing rapidly in many countries. Socioeconomic inequalities might be important for this increase. The aim of this study was to determine associations of body mass index (BMI), overweight and obesity with educational level and marital status in Chinese twins. Participants were adult twins recruited through the Chinese National Twin Registry (CNTR), aged 18 to 79 years, and the sample comprised 10,448 same-sex twin pairs. Current height, weight, educational attainment, and marital status were self-reported. Regression analyses and structural equation models were conducted to evaluate BMI, overweight, and obesity associated with educational level and marital status in both sexes. At an individual level, both educational level and marital status were associated with higher BMI and higher risk of being overweight and obesity in men, while in women the effects of educational level on BMI were in the opposite direction. In within-Monozygotic (MZ) twin-pair analyses, the effects of educational level on BMI disappeared in females. Bivariate structural equation models showed that genetic factors and shared environmental confounded the relationship between education and BMI in females, whereas marital status was associated with BMI on account of significant positive unique environmental correlation apart in both sexes. The present data suggested that marital status and BMI were associated, independent of familiar factors, for both sexes of this study population, while common genetic and shared environmental factors contributed to education-associated disparities in BMI in females.

Associations Between Obesity Indicators and Blood Pressure in Chinese Adult Twins.

Obesity is associated with blood pressure (BP), but the associations between different obesity indicators and BP have not reached agreement. Besides, both obesity and BP are influenced by genetic and environmental factors. Whether they share the same genetic or environmental etiology has not been fully understood. We therefore analyzed the relationship between different obesity indicators and BP components as well as the genetic and environmental contributions to these relationships in a Chinese adult twin sample. Twins aged 18-79 years (n = 941) were included in this study. Body mass index (BMI) was used as the index of general obesity, whereas waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) were used as the indicators of central obesity. BP components included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Linear regression models and bivariate structural equation models were used to examine the relation of various obesity indicators with BP components, and genetic or environmental influences on these associations, respectively. A strong association of BP components with BMI-and a somewhat weaker association with WC, WHtR, and WHR-was found in both sexes, independent of familial factors. Of these phenotypic correlations between obesity indicators and BP components, 60-76% were attributed to genetic factors, whereas 24-40% were attributed to unique environmental factors. General obesity was most strongly associated with high BP in Chinese adult twins. There were common genetic backgrounds for obesity and BP, and unique environmental factors also played a role.

The association of cigarette smoking and alcohol drinking with body mass index: a cross-sectional, population-based study among Chinese adult male twins.

BACKGROUND: Obesity is a multifactorial abnormality which has an underlying genetic control but requires environmental influences to trigger. Numerous epidemiological studies have examined the roles of physical inactivity and dietary factors in obesity development. Interactions between obesity-related genes and these lifestyles have also been confirmed. However, less attention has been paid to these complex relationship between cigarette smoking, alcohol drinking and obesity. The purpose of this study was to assess whether cigarette smoking and alcohol drinking were associated with body mass index (BMI), and whether these lifestyle factors modified the genetic variance of BMI. METHODS: Subjects were twins recruited through the Chinese National Twin Registry, aged 18 to 79 years, and the sample comprised 6121 complete male twin pairs. Information on height, weight, cigarette smoking and alcohol drinking status were assessed with self-report questionnaires. The associations of cigarette smoking and alcohol drinking with BMI were evaluated by linear regression models. Further, structure equation models were conducted to estimate whether cigarette smoking and alcohol drinking status modified the degree of genetic variance of BMI. RESULTS: After adjustment for a variety of socio-demographic and lifestyle factors, former smokers had higher BMI (ß = 0.475; 95 % CI, 0.196 to 0.754) whereas moderate to heavy smokers had lower BMI (ß = -0.115; 95 % CI, -0.223 to -0.007) when compared with nonsmokers. BMI decreased with increased cigarette pack-years (ß = -0.008; 95 % CI, -0.013 to -0.003). These effects still existed substantially in within-MZ twin pair analyses. By contrast, current alcohol drinking had no significant influence on BMI when additionally controlled for shared factors in within-pair analyses. Genetic modification by alcohol drinking was statistically significant for BMI (ß = -0.137; 95 % CI, -0.215 to -0.058), with the intake of alcohol decreasing the additive genetic component of BMI. CONCLUSIONS: Cigarette smoking was negatively associated with BMI independent of genetic influences. The influence of genes on BMI was moderated by alcohol drinking, such that for individuals who were regular drinkers, genetic factors became less influential. Our findings highlight gene-alcohol interaction in finding candidate genes of BMI and elucidating the etiological factors of obesity.

Genetic and Environmental Influences on Obesity-Related Phenotypes in Chinese Twins Reared Apart and Together.

The relative importance of genetic and environmental influences on obesity-related phenotypes remains unclear, and few studies have targeted the Chinese population. Here, we used Chinese twins reared apart and together to explore genetic and environmental influences on body mass index (BMI), waist circumference (WC) and waist-height ratio (WHtR), further to differentiate phenotype heritability between different age groups and genders separately and to differentiate influences of rearing environment and correlated environment. Phenotype heritability was calculated using the structural equation model in 11,401 twin pairs aged 25-85 years. BMI (0.70, 95 % confidence interval (CI) 0.66-0.74) of the total population was highly heritable, while WC (0.53, 95 %CI 0.50-0.57) and WHtR (0.48, 95 %CI 0.45-0.51) were moderately heritable. Age and gender stratified analyses found higher heritability in the younger group and males than the older group and females. The correlated environment had a greater influence on the phenotypes than the rearing environment, especially on WC and WHtR, indicating that more correlated environment actions should be taken to prevent the rising trend of abdominal obesity.

Genetic contribution to the variance of blood pressure and heart rate: a systematic review and meta-regression of twin studies.

The genetic contribution of blood pressure and heart rate (HR) varied widely between studies. Demographic factors such as ethnicity, age and/or sex might explain some of the heterogeneity. We performed a systematic review focusing on four phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), HR and pulse pressure (PP). Meta-regression was conducted to analyze potential factors in relation to SBP and DBP heritability. A total of 10,613 independent twins that came from 17 studies were included in the analysis. The weighted mean value of heritability for SBP and DBP was 0.54 (95% CIs: 0.48-0.60) and 0.49 (95% CIs: 0.42-0.56). Comparatively, three studies of HR and four studies of PP heritability were limited for the heterogeneity test. Meta-regression showed that, on average, SBP heritability with additive genes/unique environment (AE) model tend to have a higher heritability than additive genes/shared environment/unique environment (ACE) model (coefficient = 0.0947, p = .0142). A similar result was found for DBP as well. No other factors such as sex, age, ethnicity, publication year were significantly associated with heritability variance. Our study shows heritability estimates based on twin studies of both SBP and DBP are around 50%, using an AE rather than an ACE model; the variance due to C ended up in A, suggesting that the AE model may overestimate heritability if a small contribution of shared environment exists.

Association between epigenetic age and type 2 diabetes mellitus or glycemic traits: A longitudinal twin study.

Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) clocks representing the degree of aging and DunedinPACE representing the pace of aging. Prior studies have shown the associations between epigenetic aging and T2DM, but the results vary by epigenetic age metrics and people. This study explored the associations between epigenetic age metrics and T2DM or glycemic traits, based on 1070 twins (535 twin pairs) from the Chinese National Twin Registry. It also explored the temporal relationships of epigenetic age metrics and glycemic traits in 314 twins (157 twin pairs) who participated in baseline and follow-up visits after a mean of 4.6 years. DNA methylation data were used to calculate epigenetic age metrics, including PCGrimAge acceleration (PCGrimAA), PCPhenoAge acceleration (PCPhenoAA), DunedinPACE, and the longitudinal change rate of PCGrimAge/PCPhenoAge. Mixed-effects and cross-lagged modelling assessed the cross-sectional and temporal relationships between epigenetic age metrics and T2DM or glycemic traits, respectively. In the cross-sectional analysis, positive associations were identified between DunedinPACE and glycemic traits, as well as between PCPhenoAA and fasting plasma glucose, which may be not confounded by shared genetic factors. Cross-lagged models revealed that glycemic traits (fasting plasma glucose, HbA1c, and TyG index) preceded DunedinPACE increases, and TyG index preceded PCGrimAA increases. Glycemic traits are positively associated with epigenetic age metrics, especially DunedinPACE. Glycemic traits preceded the increases in DunedinPACE and PCGrimAA. Lowering the levels of glycemic traits may reduce DunedinPACE and PCGrimAA, thereby mitigating age-related comorbidities.

Association Between DNA Methylation and Blood Pressure: A 5-Year Longitudinal Twin Study.

BACKGROUND: Previous EWASs (Epigenome-Wide Association Studies) have reported hundreds of blood pressure (BP) associated 5'-cytosine-phosphate-guanine-3' (CpG) sites. However, their results were inconsistent. Longitudinal observations on the temporal relationship between DNA methylation and BP are lacking. METHODS: A candidate CpG site association study for BP was conducted on 1072 twins in the Chinese National Twin Registry. PubMed and EMBASE were searched for candidate CpG sites. Cross-lagged models were used to assess the temporal relationship between BP and DNA methylation in 308 twins who completed 2 surveys in 2013 and 2018. Then, the significant cross-lagged associations were validated by adopting the Inference About Causation From Examination of Familial Confounding approach. Finally, to evaluate the cumulative effects of DNA methylation on the progression of hypertension, we established methylation risk scores based on BP-associated CpG sites and performed Markov multistate models. RESULTS: 16 and 20 CpG sites were validated to be associated with systolic BP and diastolic BP, respectively. In the cross-lagged analysis, we detected that methylation of 2 CpG sites could predict subsequent systolic BP, and systolic BP predicted methylation at another 3 CpG sites. For diastolic BP, methylation at 3 CpG sites had significant cross-lagged effects for predicting diastolic BP levels, while the prediction from the opposite direction was observed at one site. Among these, 3 associations were validated in the Inference About Causation From Examination of Familial Confounding analysis. Using the Markov multistate model, we observed that methylation risk scores were associated with the development of hypertension. CONCLUSIONS: Our findings suggest the significance of DNA methylation in the development of hypertension.

Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Asymptomatic and pre-symptomatic infection in Coronavirus Disease 2019 pandemic.

With the presence of Coronavirus Disease 2019 (COVID-19) asymptomatic infections detected, their proportion, transmission potential, and other aspects such as immunity and related emerging challenges have attracted people's attention. We have found that based on high-quality research, asymptomatic infections account for at least one-third of the total cases, whereas based on systematic review and meta-analysis, the proportion is about one-fifth. Evaluating the true transmission potential of asymptomatic cases is difficult but critical, since it may affect national policies in response to COVID-19. We have summarized the current evidence and found, compared with symptomatic cases, the transmission capacity of asymptomatic individuals is weaker, even though they have similar viral load and relatively short virus shedding duration. As the outbreak progresses, asymptomatic infections have also been found to develop long COVID-19. In addition, the role of asymptomatic infection in COVID-19 remains to be further revealed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge. Nevertheless, as asymptomatic infections transmit the SARS-CoV-2 virus silently, they still pose a substantial threat to public health. Therefore, it is essential to conduct screening to obtain more knowledge about the asymptomatic infections and to detect them as soon as possible; meanwhile, management of them is also a key point in the fight against COVID-19 community transmission. The different management of asymptomatic infections in various countries are compared and the experience in China is displayed in detail.

Longitudinal Association of DNA Methylation With Type 2 Diabetes and Glycemic Traits: A 5-Year Cross-Lagged Twin Study.

Investigators of previous cross-sectional epigenome-wide association studies (EWAS) in adults have reported hundreds of 5'-cytosine-phosphate-guanine-3' (CpG) sites associated with type 2 diabetes mellitus (T2DM) and glycemic traits. However, the results from EWAS have been inconsistent, and longitudinal observations of these associations are scarce. Furthermore, few studies have investigated whether DNA methylation (DNAm) could be modified by smoking, drinking, and glycemic traits, which have broad impacts on genome-wide DNAm and result in altering the risk of T2DM. Twin studies provide a valuable tool for epigenetic studies, as twins are naturally matched for genetic information. In this study, we conducted a systematic literature search in PubMed and Embase for EWAS, and 214, 33, and 117 candidate CpG sites were selected for T2DM, HbA1c, and fasting blood glucose (FBG). Based on 1,070 twins from the Chinese National Twin Registry, 67, 17, and 16 CpG sites from previous studies were validated for T2DM, HbA1c, and FBG. Longitudinal review and blood sampling for phenotypic information and DNAm were conducted twice in 2013 and 2018 for 308 twins. A cross-lagged analysis was performed to examine the temporal relationship between DNAm and T2DM or glycemic traits in the longitudinal data. A total of 11 significant paths from T2DM to subsequent DNAm and 15 paths from DNAm to subsequent T2DM were detected, suggesting both directions of associations. For glycemic traits, we detected 17 cross-lagged associations from baseline glycemic traits to subsequent DNAm, and none were from the other cross-lagged direction, indicating that CpG sites may be the consequences, not the causes, of glycemic traits. Finally, a longitudinal mediation analysis was performed to explore the mediation effects of DNAm on the associations of smoking, drinking, and glycemic traits with T2DM. No significant mediations of DNAm in the associations linking smoking and drinking with T2DM were found. In contrast, our study suggested a potential role of DNAm of cg19693031, cg00574958, and cg04816311 in mediating the effect of altered glycemic traits on T2DM.

Cardiometabolic Traits in Adult Twins: Heritability and BMI Impact with Age.

Background: The prevalence of obesity and cardiometabolic diseases continues to rise globally and obesity is a significant risk factor for cardiometabolic diseases. However, to our knowledge, evidence of the relative roles of genes and the environment underlying obesity and cardiometabolic disease traits and the correlations between them are still lacking, as is how they change with age. Method: Data were obtained from the Chinese National Twin Registry (CNTR). A total of 1421 twin pairs were included. Univariate structural equation models (SEMs) were performed to evaluate the heritability of BMI and cardiometabolic traits, which included blood hemoglobin A1c (HbA1c), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Bivariate SEMs were used to assess the genetic/environmental correlations between them. The study population was divided into three groups for analysis: ≤50, 51−60, and >60 years old to assess the changes in heritability and genetic/environmental correlations with ageing. Results: Univariate SEMs showed a high heritability of BMI (72%) and cardiometabolic traits, which ranged from 30% (HbA1c) to 69% (HDL-C). With age increasing, the heritability of all phenotypes has different degrees of declining trends. Among these, BMI, SBP, and DBP presented significant monotonous declining trends. The bivariate SEMs indicated that BMI correlated with all cardiometabolic traits. The genetic correlations were estimated to range from 0.14 (BMI and LDL-C) to 0.39 (BMI and DBP), while the environmental correlations ranged from 0.13 (BMI and TC/LDL-C) to 0.31 (BMI and TG). The genetic contributions underlying the correlations between BMI and SBP and DBP, TC, TG, and HDL-C showed a progressive decrease as age groups increased. In contrast, environmental correlations displayed a significant increasing trend for HbA1c, SBP, and DBP. Conclusions: The findings suggest that genetic and environmental factors have essential effects on BMI and all cardiometabolic traits. However, as age groups increased, genetic influences presented varying degrees of decrement for BMI and most cardiometabolic traits, suggesting the increasing importance of environments. Genetic factors played a consistently larger role than environmental factors in the phenotypic correlations between BMI and cardiometabolic traits. Nevertheless, the relative magnitudes of genetic and environmental factors may change over time.