Ferroptosis defense mechanisms: The future and hope for treating osteosarcoma.

Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron-dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano-drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions.

Temporal associations between leukocytes DNA methylation and blood lipids: a longitudinal study.

BACKGROUND: The associations between blood lipids and DNA methylation have been investigated in epigenome-wide association studies mainly among European ancestry populations. Several studies have explored the direction of the association using cross-sectional data, while evidence of longitudinal data is still lacking. RESULTS: We tested the associations between peripheral blood leukocytes DNA methylation and four lipid measures from Illumina 450 K or EPIC arrays in 1084 participants from the Chinese National Twin Registry and replicated the result in 988 participants from the China Kadoorie Biobank. A total of 23 associations of 19 CpG sites were identified, with 4 CpG sites located in or adjacent to 3 genes (TMEM49, SNX5/SNORD17 and CCDC7) being novel. Among the validated associations, we conducted a cross-lagged analysis to explore the temporal sequence and found temporal associations of methylation levels of 2 CpG sites with triglyceride and 2 CpG sites with high-density lipoprotein-cholesterol (HDL-C) in all twins. In addition, methylation levels of cg11024682 located in SREBF1 at baseline were temporally associated with triglyceride at follow-up in only monozygotic twins. We then performed a mediation analysis with the longitudinal data and the result showed that the association between body mass index and HDL-C was partially mediated by the methylation level of cg06500161 (ABCG1), with a mediation proportion of 10.1%. CONCLUSIONS: Our study indicated that the DNA methylation levels of ABCG1, AKAP1 and SREBF1 may be involved in lipid metabolism and provided evidence for elucidating the regulatory mechanism of lipid homeostasis.

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.

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.

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.

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.

Associations of Metabolic/Obesity Phenotypes with Insulin Resistance and C-Reactive Protein: Results from the CNTR Study.

BACKGROUND: Obesity is a heterogeneous condition in terms of metabolic status. Different obesity phenotypes have various health risks. The aim of this work was to define different subtypes of obesity and investigate their relationship with inflammatory-cardiometabolic abnormalities among Chinese adult twins. METHODS: The analyses used data from 1113 adult twins in 4 provinces (Shandong, Zhejiang, Jiangsu and Sichuan) from Chinese National Twin Registry (CNTR) which collected detailed information. We defined those with 0 or 1 metabolic syndrome (MetS) components excluding waist circumference as metabolically healthy, and those with waist circumference ≥90 cm (for men) and ≥85 cm (for women) as obese. The two-category obesity status and metabolic states are combined to generate four metabolic/obesity phenotypes. High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as surrogate measure of insulin resistance. Mixed-effect linear regression models and fixed-effect linear regression models were used to analyse the correlation between HOMA-IR, hsCRP and different metabolic/obesity phenotypes. RESULTS: In cross-sectional analyses of 1113 individuals (mean [SD] age, 46.6 [12.9] years; 463 obese [41.6%]), 20.3% obese twins were metabolic healthy and 64.2% non-obese twins were metabolic unhealthy. Serum HOMA-IR level was higher in metabolically unhealthy non-obesity (MUNO) (ß=0.42, 95% CI: 0.21-0.64), metabolically healthy obesity (MHO) (ß=0.68, 95% CI: 0.36-1.00) and metabolically unhealthy obesity (MUO) (ß=0.69, 95% CI: 0.46-0.91) twins, compared with their metabolically healthy non-obesity (MHNO) counterparts. HsCRP was similar between MHO and MUO, which differed significantly to metabolic healthy non-obesity (MHNO). CONCLUSION: MHO and MUNO phenotypes were common in Chinese twin population. Both phenotypes were associated with elevated IR and hsCRP which may not be benign and need to be concerned.

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.

[A co-twin control study on birth weight, overweight and obesity among children younger than 18 years old in China].

OBJECTIVE: To analyze the associations between birth weight and overweight/obesity among children. METHODS: A total of 8 267 twin pairs younger than 18 years old from the Chinese National Twin Registry were included in the study. Associations between birth weight, childhood BMI and overweight/obesity were explored by this co-twin control study. RESULTS: After adjusting for sex and zygosity, when birth weight had an increase of 0.5 kg per fold, the OR values for overweight and obesity were 1.87(95%CI: 1.40-2.48) for 2-6 year olds, 1.69 (95%CI: 1.16-2.46) for 6-12 year olds and 1.28 (95%CI: 0.80-2.07) for 12-18 year olds. RESULTS: from the stratified analysis in the 2-6 year-olds, statistically significant differences were seen. When birth weight increased 0.5 kg per fold, the risk of overweight and obesity increased by 0.87 times among the dizygotic twins, more than that of the monozygotic twins (OR=1.86, 95%CI:1.24-2.81). The risk for male twins was 1.12 times higher than that of female twins (OR=1.65, 95%CI:1.11-2.44). CONCLUSIONS: Birth weight seemed associated with overweight and obesity for kids at early childhood or at age for schools. However, guidance on the implementation of public health interventions is still needed on these children.

Physical activity attenuates genetic effects on BMI: Results from a study of Chinese adult twins.

OBJECTIVE: This study aimed to examine the gene-environment interaction of physical activity and body mass index (BMI) using the Chinese National Twin Registry (CNTR). METHODS: A total of 19,308 same-sex adult twins from CNTR were included in the analysis. Twin zygosity was determined by self-reported questionnaire. Height and weight were measured using self-reported questionnaire. The vigorous physical activity was defined as greater or equal to five times a week of at least 30 min moderate- or high-intensity physical activity. A twin structural equation model was used to analyze the gene-environment interaction of vigorous exercise with BMI among 13,506 monozygotic twins and 5,802 dizygotic twins. RESULTS: A structural equation model adjusting for age and sex found vigorous exercise significantly moderated the additive genetic effects (P < 0.001) and shared environmental effects (P < 0.001) on BMI. The genetic contributions to BMI were significantly lower for people who adopted a physically active lifestyle [h(2) = 40%, 95% confidence interval (CI): 35%-46%] than those who were relative sedentary (h(2) = 59%, 95% CI: 52%-66%). The observed gene-physical activity interaction was more pronounced in men than women. CONCLUSIONS: Our results suggested that adopting a physically active lifestyle may help to reduce the genetic influence on BMI among the Chinese population.

Inhalation Study of Mycobacteriophage D29 Aerosol for Mice by Endotracheal Route and Nose-Only Exposure.

BACKGROUND: Lytic mycobacteriophage D29 has the potential for tuberculosis treatment including multidrug-resistant strains. The aims of this study are to investigate deposition and distribution of aerosolized phage D29 particles in naive Balb/C mice, together with pharmacokinetics and evaluation of acute lung injury. METHODS: Pharmacokinetics and BALF (bronchoalveolar lavage fluids) were analyzed after administration of phage D29 aerosols by endotracheal route using Penn-century aerosolizer; Collison 6-jet and Spinning top aerosol nebulizers (STAG) were used to generate phage aerosols with different particle size distributions in nose-only inhalation experiments. After exposure, deposited amounts of phage D29 particles in respiratory tracts were measured, and deposition efficiencies were calculated. A typical path deposition model for mice was developed, and then comparisons were made between predictions and experimentally measured results. RESULTS: Approximately 10% of aerosolized phages D29 reached lung of mouse for pulmonary delivery, and were completely eliminated until 72 h after administration. In contrast, about 0.1% of intraperitoneal injected phages reached the lung, and were almost eliminated at 12 h time point. The inflammation was hardly observed in lung according to the results of BALF analysis. The CMADs (count median aerodynamic diameters) of generated aerosol by Collison and STAG nebulizer were 0.8 µm and 1.5 µm, respectively. After nose-only exposure, measured deposition efficiencies in whole respiratory tract for 0.8 and 1.5 µm phage particles were below 1% and 10%, respectively. Predictions of the computer deposition model compared fairly well with experimentally measured results. CONCLUSIONS: This is the first systematic study of phage D29 aerosol respiratory challenge in laboratory animals. It provides evidence that aerosol delivery of phage D29 is an effective way for treating pulmonary infections caused by Mycobacterium tuberculosis. This research will also provide important data for future inhalation experiments.

Associations of Body Composition Measurements with Serum Lipid, Glucose and Insulin Profile: A Chinese Twin Study.

OBJECTIVES: To quantitate and compare the associations of various body composition measurements with serum metabolites and to what degree genetic or environmental factors affect obesity-metabolite relation. METHODS: Body mass index (BMI), waist circumference (WC), lean body mass (LBM), percent body fat (PBF), fasting serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), glucose, insulin and lifestyle factors were assessed in 903 twins from Chinese National Twin Registry (CNTR). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting serum glucose and insulin. Linear regression models and bivariate structural equation models were used to examine the relation of various body composition measurements with serum metabolite levels and genetic/environmental influences on these associations, respectively. RESULTS: At individual level, adiposity measurements (BMI, WC and PBF) showed significant associations with serum metabolite concentrations in both sexes and the associations still existed in male twins when using within-MZ twin pair comparison analyses. Associations of BMI with TG, insulin and HOMA-IR were significantly stronger in male twins compared to female twins (BMI-by-sex interaction p = 0.043, 0.020 and 0.019, respectively). Comparison of various adiposity measurements with levels of serum metabolites revealed that WC explained the largest fraction of variance in serum LDL-C, TG, TC and glucose concentrations while BMI performed best in explaining variance in serum HDL-C, insulin and HOMA-IR levels. Of these phenotypic correlations, 64-81% were attributed to genetic factors, whereas 19-36% were attributed to unique environmental factors. CONCLUSIONS: We observed different associations between adiposity and serum metabolite profile and demonstrated that WC and BMI explained the largest fraction of variance in serum lipid profile and insulin resistance, respectively. To a large degree, shared genetic factors contributed to these associations with the remaining explained by twin-specific environmental factors.

Genetic and Environmental Effects on Weight, Height, and BMI Under 18 Years in a Chinese Population-Based Twin Sample.

This study examined the genetic and environmental effects on variances in weight, height, and body mass index (BMI) under 18 years in a population-based sample from China. We selected 6,644 monozygotic and 5,969 dizygotic twin pairs from the Chinese National Twin Registry (CNTR) aged under 18 years (n = 12,613). Classic twin analyses with sex limitation were used to estimate the genetic and environmental components of weight, height, and BMI in six age groups. Sex-limitation of genetic and shared environmental effects was observed, especially when puberty begins. Heritability for weight, height, and BMI was low at 0-2 years old (less than 20% for both sexes) but increased over time, accounting for half or more of the variance in the 15-17 year age group for boys. For girls, heritabilities for weight, height and BMI was maintained at approximately 30% after puberty. Common environmental effects on all body measures were high for girls (59-87%) and presented a small peak during puberty. Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in the pre-adolescent period and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. Further studies about puberty-related genes and social environment are needed to clarify the mechanism of sex differences.

Determination of Zygosity in Adult Chinese Twins Using the 450K Methylation Array versus Questionnaire Data.

Previous studies have shown that both single nucleotide polymorphisms (SNPs) and questionnaires-based method can be used for twin zygosity determination, but few validation studies have been conducted using Chinese populations. In the current study, we recruited 192 same sex Chinese adult twin pairs to evaluate the validity of using genetic markers-based method and questionnaire-based method in zygosity determination. We considered the relatedness analysis based on more than 0.6 million SNPs genotyping as the golden standards for zygosity determination. After quality control, qualified twins were left for relatedness analysis based on identical by descent calculation. Then those same sex twin pairs were included in the zygosity questionnaire validation analysis. Logistic regression model was applied to assess the discriminant ability of age, sex and the three questions in zygosity determination. Leave one out cross-validation was used as a measurement of internal validation. The results of zygosity determination based on 65 SNPs in 450k methylation array were all consistent with genotyping. Age, gender, questions of appearance confused by strangers and previously perceived zygosity consisted of the most predictable model with a consistency rate of 0.8698, cross validation predictive error of 0.1347. For twin studies with genotyping and\or 450k methylation array, there would be no need to conduct other zygosity testing for the sake of costs consideration.

[Heritability of body mass index on Chinese adult twins from nine provinces/cities in China].

OBJECTIVE: To explore the heritability of body mass index (BMI) in twins across different regions and genders in China. METHODS: A total of 11 122 adult twin pairs from the Chinese National Twin Registry were interviewed. A structural equation model was used to estimate the heritability of BMI. RESULTS: This study included 6 226 monozygotic twin pairs and 4 896 dizygotic twin pairs, with the age range as 25-85 (39.0 ± 10.8) years. Under stratified analysis by region, results showed that the highest and lowest rates on heritability of BMI in men were seen in Tianjin and Zhejiang, as 67.8% (95% CI: 50.1%-85.8%) and 42.1% (95% CI: 27.2%-60.9%), while in women were seen in Sichuan and Heilongjiang as 56.2% (95% CI: 47.5%-70.0%) and 11.2% (95% CI: 0.0%-31.7%), respectively. Results from the stratified analysis showed that, by gender, the heritability of BMI in men was higher than that in women from the same region. The biggest differences of heritability of BMI between men and women were seen in Heilongjiang as 55.3% (95% CI: 35.5%-80.0%) and 11.2% (95% CI: 0-31.7%), while the smallest differences were seen in Sichuan as 61.5% (95% CI: 40.7%-86.4%) and 56.2% (95% CI: 47.5%-70.0%), respectively. CONCLUSION: The heritability of BMI across different regions and genders showed certain differences in the Chinese twins.

[Change trend of birth weight of twins in China, 1995-2012].

OBJECTIVE: To understand the change trend of birth weight of twins in China from 1995 to 2012. METHODS: A total of 10 827 twins born between 1995 and 2012 registered in national twin registry system in 8 provinces in China were included in this study. A retrospective study was conducted to analyze the change trend of twin's birth weight. RESULTS: Mean birth weight of twins decreased by 0.01 kg every five years after adjusting sex, ovum type and place of birth (P = 0.041). The birth weight decreased both in superior twin and in inferior twin over time. After 2007, the birth weight of superior twin decreased by 0.008 kg each year, while the birth weight of inferior twin decreased by 0.014 kg each year. Mean relative difference in birth weight and birth weight discordant rate decreased before 2002, then increased from the lowest point 8.16% and 16.20% to highest point 9.99% and 22.40% respectively. CONCLUSION: The birth weight of twins in China decreased between 1995 and 2012, while the birth weight discordant rate increased, suggesting that close attention should be paid to the discordance of twin body weight to reduce the risk of adverse health outcome.

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.