Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study.

Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.

Association between fresh fruit consumption and the risk of chronic obstructive pulmonary disease-related hospitalization and death in Chinese adults: A prospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China.@*METHODS@#Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders.@*RESULTS@#During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively.@*CONCLUSIONS@#High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.

Study on the association between the efficacy of peg-IFN and the complexity of TP and RT in chronic hepatitis B / 中华实验和临床病毒学杂志

Objective@#To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B.@*Methods@#Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation.@*Results@#Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response.@*Conclusions@#The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.

Functional study on plasmacytoid dendritic cells in patients with HBeAg-positive chronic hepatitis B treated with entecavir / 中华实验和临床病毒学杂志

Objective@#To investigate the correlation between the frequency and function of early plasmacytoid dendritic cells (pDC) and the treatment response in patients with HBeAg-positive chronic hepatitis B receiving entecavir (ETV).@*Methods@#Patients with HBeAg-positive chronic hepatitis B were enrolled. Antiviral therapy with ETV, serum serological markerso hepatitis B virs (HBV) infection and liver function (HBV DNA load, HBsAg/anti-HBs, HBeAg and anti-HBe levels, and ALT levels) were monitored every three months before and during treatment; the efficacy of ETV was assessed by changes in the level of HBV DNA. Peripheral venous blood was collected before treatment, at 12 weeks and 24 weeks, respectively. Flow cytometry was used to detect the frequency of peripheral blood pDC and the surface co-stimulatory molecule CD86. The baseline and early treatment (12 weeks and 24 weeks) pDC frequency and functional changes were analyzed.@*Results@#Of the 100 patients with chronic hepatitis B, 45 patients received ETV treatment and 48 weeks of follow-up. Within 48 weeks of ETV treatment, HBsAg levels decreased by 0.53±0.78 log IU/mL; HBeAg decreased by 816.61S/CO, and HBeAg seroconversion occurred in 4 cases; HBV DNA content decreased by 6.04±1.12 log IU/mL, in 33 cases (73%) the HBV DNA became undetectable, in 43 cases ALT kept normal continuously for more than 3 months. In the early stage of ETV treatment, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes. In ETV-treated HBV DNA responders, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes; HBV DNA non-responders had a significant increase in pDC%, but CD86+ pDC% decreased significantly, and CD86MFI and CD86ABC showed no significant changes. The decrease in HBsAg and HBeAg levels in ETV treated patients was not significantly associated with early pDC%, CD86+ pDC%, CD86MFI and CD86ABC changes.@*Conclusions@#ETV treatment can directly inhibit the replication of HBV DNA, but does not enhance the function of immune cells.

Analysis on the heritability of diabetes, based on data from the Chinese adult twins / 中华流行病学杂志

Objective@#To analyze the heritability of diabetes among the Chinese twin adults.@*Methods@#A total of 10 253 same-sex twin pairs aged 25 years and older, were selected from the Chinese National Twin Registry (CNTR) program. Heritability of diabetes was calculated by using the structural equation model.@*Results@#After adjusted for age and gender, the overall heritability rates of diabetes were 0.41 (0.15-0.75), 0.83 (0.72-0.91) and 0.34 (0.04-0.73) in the <45 and ≥45 years twin pairs, respectively. After adjusted for age, rates of heritability appeared as 0.37 (0.05-0.78) and 0.88 (0.79-0.94) in men and women, respectively.@*Conclusions@#Diabetes is affected by both genetic and environmental factors. The genetic effect of diabetes seemed stronger on female than that on male twins but was dying down along with ageing.

Effect of family environment in childhood and adolescence on mental health in adulthood / 中华流行病学杂志

Objective To explore the relationship of family environment in childhood and adolescence and mental health in adulthood.Methods A total of 791 subjects aged ≥25 years were selected through the Chinese National Twin Registry (CNTR).The short-form of Family Environment Scale-Chinese Version (FES-CV) was used to evaluate the family environment during childhood and adolescence in three dimensions:relationship,system maintenance and personal growth.The mental health status in adulthood was assessed with the Chinese version of 6-item Kessler Psychological Distress Scale (K6).The generalized linear mixed model was used to examine their relationship.Results About 4.6％ of the subjects reported general or worse mental health status.Compared with the subjects with good mental status,statistical difference was observed only in parenting way among twins (living together or not).After adjusting the potential confounders,such as age,sex,zygosity,education and lifestyle (smoking,drinking and physical activity),good family relationship and system maintenance had a positive effect on mental health,with the OR (95％CI) of 0.66 (0.5 1-0.87) and 0.70 (0.50-0.98) respectively.Furthermore,parenting way did not modify the effect of family environment on mental health status in adulthood (interaction:P＞0.05).In each scale,scores of cohesion and organization were positively correlated with mental health,while the score of conflict was negatively correlated with the mental health.Conclusion Good family relationship and system maintenance in childhood and adolescence had a positive impact on mental health in adulthood.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective On whole-genome scale,we tried to explore the correlation between obesity-related traits and DNA methylation sites,based on discordant monozygotic twin pairs.Methods A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district,Yanqing district and Fangshan district in Beijing in 2016.Information on twins was gathered through a self-designed questionnaire and results from physical examination,including height,weight and waist circumference of the subjects under study.DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip.R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes.Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs).VarFit function of emp irical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups.Results According to the obesity discordance criteria,we collected 23 pairs of twins (age range 7 to 16 years),including 12 male pairs.A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis.According to the significance level of FDR set as ＜0.05,no positive sites would meet this standard.When DMC CpG site cg05684382,with the smallest P value (1.26E-06) as on chromosome 12,the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16.Conclusions In this study,we analyzed the genome-wide DNA methylation and its correlation with obesity traits.After multiple testing corrections,no positive sites were found to have associated with obesity.However,results from the correlation analysis demonstrated sites cg05684382 (chr:12) and cg26188191 (chr:16) might have played a role in the development of obesity.This study provides a methodologic reference for the studies on discordance twins related problems.

Fujian Tulou Family Cohort Study: study design and characteristics of participants and pedigrees in baseline investigation / 中华流行病学杂志

Objective To describe the study design,the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study.Methods Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank.A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018,including questionnaire survey,physical and biochemical indicators examinations,and blood sample collection in adults aged ≥ 18 years.In addition,family relationship of the participants was also recorded.The pedigree information of the juveniles under 18 years old were also collected.Results The baseline survey included 2 727 individuals in two clans,of whom 2 373 (87.0％) were adults,and 2 126 participants completed questionnaires,physical examinations and biochemical tests.The average age of the 2 126 participants was (57.9 ± 13.3) years,with 39.4％ being males.The current smoking rates in male and female participants were 41.2％ and 2.1％,respectively.The corresponding rates of current alcohol consumption were 19.0％ and 2.6％.For common chronic diseases,the prevalence rates were 51.3％ for hypertension,9.7％ for diabetes and 26.7％ for hyperlipemia according to the self-reported disease diagnoses,health examination results and biochemical examination results in class 1Ⅱor Ⅲ hospitals.Based on the family relationship information and genealogical data,710 pedigrees were finally identified,consisting of 5 087 family members.The numbers of five,four,three,and two generations pedigrees were 3,88,238 and 381,respectively.The pairs of the first to the fifth degree relatives were 12 039,2 662,1 511,202 and 31,respectively.Conclusion The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors,environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

Epidemiological characteristics of household fuel use in 10 areas of China / 中华流行病学杂志

Objective To describe the characteristics of cooking and heating fuel use in participants from the China Kadoorie Biobank (CKB) study.Methods The CKB study recruited 512 891 adults from 10 areas in China during 2004-2008.Information on cooking fuel and heating fuel was collected using a questionnaire in baseline survey.The proportions of various fuels used in different areas,in different populations,and at different time points were calculated and compared.Results Overall,52.1％ participants used solid fuel for cooking or heating.Rural areas had higher prevalence of solid fuel use than urban areas.The percentage of participants using solid fuel for cooking was 36.1％ (coal 20.1％,wood/charcoal 16.0％);The percentage of participants using solid fuel for heating was 36.7％ (coal 22.7％,wood/charcoal 14.0％).The prevalence of solid fuel use and the fuel type mainly used varied widely across 10 areas.The proportion of clean fuel use was lower in less-educated and lower-income people.Household coal and wood/charcoal use showed a declining trend,which was more remarkable in urban areas.Conclusion There are still a large number of rural residents and people with low income relying on solid fuel in China,which is a serious public health concern.

Natural killer cells function in acute and chronic hepatitis B patients / 中华实验和临床病毒学杂志

Objective@#To investigate the differences in frequency and function of natural killer cells (NK) between chronic hepatitis B (CHB) and acute hepatitis B (AHB).@*Methods@#Patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of NK, CD56dimNK, CD56brightNK and the expression of functional molecules IFNAR2 and NKp46 on the surface of NK cells were detected respectively among patients with CHB in IA phase, patients with AHB, and those recovered from AHB. At the same time, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#Between IA and AHB, the frequencies of NK cells and NKp46dim NK cells in AHB cases were significantly lower than those in IA cases, but the frequency of NKp46high NK cells in AHB was higher than that in IA. For patients who recovered from AHB, the frequency of NK cells and NKp46dim NK cells increased; the varied ranges of frequencies of CD56dimNK, IFNAR2+ NK and NKp46+ NK cells were on the rise, while the frequency of NKp46high NK cells decreased after the recovery from AHB, and the varied ranges of CD56brightNK and IFNAR2MFI, NKp46MFI decreased. In AHB, HBVDNA loads were positively correlated with ALT levels. Before and after the recovery of AHB: ΔHBV DNA and ΔALT, Δ NK/LY (%) were positively correlated; ΔALT and ΔNKp46highNK/NK(%), ΔNKp46MFI, ΔIFNAR2MFI were positively correlated.@*Conclusions@#In CHB immune active phase, the activity of peripheral blood NK cells was too weak to remove the virus, but NK cells play an important role in eliminating the viruses and mediating liver tissue inflammation in AHB.

Re-treatment with peginterferon-ribavirin and direct antiviral agents of patients with chronic hepatitis C after failure of intensified treatment / 中华实验和临床病毒学杂志

Objective@#To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.@*Methods@#Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.@*Results@#The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.@*Conclusions@#The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Effect of family environment in childhood and adolescence on mental health in adulthood / 中华流行病学杂志

Objective: To explore the relationship of family environment in childhood and adolescence and mental health in adulthood. Methods: A total of 791 subjects aged ≥25 years were selected through the Chinese National Twin Registry (CNTR). The short-form of Family Environment Scale-Chinese Version (FES-CV) was used to evaluate the family environment during childhood and adolescence in three dimensions: relationship, system maintenance and personal growth. The mental health status in adulthood was assessed with the Chinese version of 6-item Kessler Psychological Distress Scale (K6). The generalized linear mixed model was used to examine their relationship. Results: About 4.6% of the subjects reported general or worse mental health status. Compared with the subjects with good mental status, statistical difference was observed only in parenting way among twins (living together or not). After adjusting the potential confounders, such as age, sex, zygosity, education and lifestyle (smoking, drinking and physical activity), good family relationship and system maintenance had a positive effect on mental health, with the OR (95%CI) of 0.66 (0.51-0.87) and 0.70 (0.50-0.98) respectively. Furthermore, parenting way did not modify the effect of family environment on mental health status in adulthood (interaction: P>0.05). In each scale, scores of cohesion and organization were positively correlated with mental health, while the score of conflict was negatively correlated with the mental health. Conclusion: Good family relationship and system maintenance in childhood and adolescence had a positive impact on mental health in adulthood.

Epidemiological characteristics of household fuel use in 10 areas of China / 中华流行病学杂志

Objective: To describe the characteristics of cooking and heating fuel use in participants from the China Kadoorie Biobank (CKB) study. Methods: The CKB study recruited 512 891 adults from 10 areas in China during 2004-2008. Information on cooking fuel and heating fuel was collected using a questionnaire in baseline survey. The proportions of various fuels used in different areas, in different populations, and at different time points were calculated and compared. Results: Overall, 52.1% participants used solid fuel for cooking or heating. Rural areas had higher prevalence of solid fuel use than urban areas. The percentage of participants using solid fuel for cooking was 36.1% (coal 20.1%, wood/charcoal 16.0%); The percentage of participants using solid fuel for heating was 36.7% (coal 22.7%, wood/charcoal 14.0%). The prevalence of solid fuel use and the fuel type mainly used varied widely across 10 areas. The proportion of clean fuel use was lower in less-educated and lower-income people. Household coal and wood/charcoal use showed a declining trend, which was more remarkable in urban areas. Conclusion: There are still a large number of rural residents and people with low income relying on solid fuel in China, which is a serious public health concern.

Association between obesity and DNA methylation among the 7-16 year-old twins / 中华流行病学杂志

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.

Fujian Tulou Family Cohort Study: study design and characteristics of participants and pedigrees in baseline investigation / 中华流行病学杂志

Objective: To describe the study design, the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study. Methods: Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank. A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018, including questionnaire survey, physical and biochemical indicators examinations, and blood sample collection in adults aged ≥18 years. In addition, family relationship of the participants was also recorded. The pedigree information of the juveniles under 18 years old were also collected. Results: The baseline survey included 2 727 individuals in two clans, of whom 2 373 (87.0%) were adults, and 2 126 participants completed questionnaires, physical examinations and biochemical tests. The average age of the 2 126 participants was (57.9±13.3) years, with 39.4% being males. The current smoking rates in male and female participants were 41.2% and 2.1%, respectively. The corresponding rates of current alcohol consumption were 19.0% and 2.6%. For common chronic diseases, the prevalence rates were 51.3% for hypertension, 9.7% for diabetes and 26.7% for hyperlipemia according to the self-reported disease diagnoses, health examination results and biochemical examination results in class Ⅱ or Ⅲ hospitals. Based on the family relationship information and genealogical data, 710 pedigrees were finally identified, consisting of 5 087 family members. The numbers of five, four, three, and two generations pedigrees were 3, 88, 238 and 381, respectively. The pairs of the first to the fifth degree relatives were 12 039, 2 662, 1 511, 202 and 31, respectively. Conclusion: The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors, environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

Functions of NK cells in chronic hepatitis B patients treated with interferon / 中华实验和临床病毒学杂志

Objective@#To elucidate the functions of peripheral blood NK cells in chronic hepatitis B patients treated with interferon.@*Methods@#Venous whole blood samples were obtained from patients in the immune clearance (IC) phase treated with peg-interferon-alpha-2a (Peg-IFNα-2a) at baseline (t=0), 12 weeks (t=12) and 24 weeks (t=24). The frequencyies of peripheral blood CD3-CD56+ NK cells, CD56brightNK cells and CD56dimNK cells, the expression level of IFNAR2 and NKp46 on NK cells were detected by flow cytometry. The levels of serum HBV DNA, HBsAg, HBeAg and ALT were detected by Ditan Hospital clinical laboratory.@*Results@#Forty-one patients in the IC phase treated with Peg-IFNα-2a, including 21 poor response (PR) patients and 20 good response (GR) patients, were recruited for this study. Theresult were as follows: The frequency of peripheral blood CD3-CD56+ NK cells was increased at week 24 in GR compared with the baseline(11.74, 5.69%-18.15% vs 13.7, 9.36-20.18%, P>0.05), and it also was increased in PR(8.94, 6.26%-14.15% vs 12.5, 7.64-16.55%, P>0.05). The frequency of peripheral blood CD56brightNK cells was increased at week 24 in GR compared with the baseline(9.49, 6.2%-12.48% vs 12.98, 7.75%-20.93%, P>0.05), and it also was increased in PR(11.45, 8.27%-19.13% vs 17.52, 12.3%-22.42%, P=0.0239). The expression level of NKp46 on NK cells was significantly increased at week 24 in GR compared with the baseline(90.55, 83.8-94.78 vs 93.8, 92.28-96.4, P=0.0263), but it was not increased in PR(95, 90.6-96.15 vs 94.3, 92.1-95.6, P>0.05). The expression level of NKp46high on NK cells was significantly increased at week 24 in GR compared with the baseline(12.4, 8.58-19.08 vs 39.3, 23.15-49.3, P=0.0011), at that range of the increase was significantly higher than PR(14.2, 9.78-17.65 vs 27.58, 19.13-36.56, P=0.006).@*Conclusions@#The frequencies of peripheral blood CD3-CD56+ NK cells and CD56brightNK cells were increased from patients in the IC phase treated with Peg-IFNα-2a. The expression level of NKp46 on NK cells was increased in GR patients treated with Peg-IFNα-2a. The expression level of NKp46high on NK cells was significantly increased, especially in GR patients treated with Peg-IFNα-2a.

Association between birth cohort and the heritability of body mass index / 中华流行病学杂志

Objective To investigate the varying variances of the genetic components in birth cohorts.Methods Twin samples used in the current study were collected from the Chinese National Twin Registry and a two-wave study was conducted,in Qingdao and Lishui regions.Samples were broken down by birth cohort to create four subgroups:-1958,1959-1961,1962-1970 and 1970-.Structural equation models were fitted in each subgroup to estimate the genetic and environmental variances.Results From each birth cohort,weight and body mass index in 2012 appeared higher than those in 2001.Twins of 1971-cohort subgroup showed lower weight than in the other cohort subgroups.Except for the 1959-1961 cohort subgroup,the later birth cohorts were inversely related to the body mass indexes.Genetic factors might explain 54％-76％ of the total variations on the body mass index.Heritability of body mass index of twins born during 1959-1961 was increasing along with age.Conclusion Genetic factors might explain the main portion which related to the phenotypic variance of body mass index.Effects of genetic factors on body mass index of twins born during 1959-1961 might have increased along with age.

Association between birth cohort and the heritability of body mass index / 中华流行病学杂志

Objective To investigate the varying variances of the genetic components in birth cohorts.Methods Twin samples used in the current study were collected from the Chinese National Twin Registry and a two-wave study was conducted,in Qingdao and Lishui regions.Samples were broken down by birth cohort to create four subgroups:-1958,1959-1961,1962-1970 and 1970-.Structural equation models were fitted in each subgroup to estimate the genetic and environmental variances.Results From each birth cohort,weight and body mass index in 2012 appeared higher than those in 2001.Twins of 1971-cohort subgroup showed lower weight than in the other cohort subgroups.Except for the 1959-1961 cohort subgroup,the later birth cohorts were inversely related to the body mass indexes.Genetic factors might explain 54％-76％ of the total variations on the body mass index.Heritability of body mass index of twins born during 1959-1961 was increasing along with age.Conclusion Genetic factors might explain the main portion which related to the phenotypic variance of body mass index.Effects of genetic factors on body mass index of twins born during 1959-1961 might have increased along with age.

Mendelian randomization analysis of the relationship between obesity and DNA methylation / 中华预防医学杂志

Objective@#To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis.@*Methods@#A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status. Association analyses between DNA methylation and BMI and between CpGs and cis-SNP were conducted. With rs748212 as the instrumental variable, the association between cg15053022 and BMI was explored using the Mendelian randomization method.@*Results@#A total of 469 participants were selected. The mean age of participants was (44.8±13.2) years and the BMI was (25.0±3.8) kg/m2. Nine BMI-related DNA methylation sites were found and DNA methylation site cg15053022 in the ATP4A gene was negatively associated with cis-SNP rs748212 (β=-0.020); the mean methylation level of AA, AC, and CC were 0.212±0.025, 0.242±0.024, and 0.264±0.028, respectively. rs748212 was associated with BMI (β=0.04, P=0.007) and closely related to cg15053022 (F=237.66, P=0.143). Mendelian randomization analysis showed lower methylation levels at cg15053022 were associated with higher BMI (β=-1.97, P<0.001).@*Conclusion@#This study supported the impact of cg15053022 methylation in the ATP4A gene on BMI using Mendelian randomization analysis and provided the basis for using Mendelian randomization analysis in methylation studies.