Wenjing Gao

Genetic and environmental influences on blood pressure and body mass index in Han Chinese : a twin study

The familial aggregation of blood pressure (BP) may be partly due to the familial aggregation of obesity, caused by genetic and/or environmental factors that influence both. Gene–obesity interactions are expected to result in different heritability estimates for BP at different obesity levels. However, the latter hypothesis has never been tested. The present study included 1243 monozygotic and 833 dizygotic Han Chinese twins (mean±s.d. age: 37.81±9.82; range: 19.1–81.4) from the Chinese National Twin Registry. Body mass index (BMI) was used as the index of general obesity. The outcome measures were systolic BP (SBP) and diastolic BP (DBP). Quantitative genetic modeling was performed using Mx software. The SBP and DBP heritabilities were 46 and 30%, respectively. The positive correlations of BMI with SBP (r=0.26) and with DBP (r=0.27) were largely due to genetic factors (approximately 85%). Genetic factors, which also influence BMI, account for 6 and 7% of the total variance for SBP and DBP, respectively. The gene–obesity interaction analysis showed that both common and unique environmental influences on SBP increased with increasing levels of BMI, resulting in a lower heritability at higher BMI levels, whereas for DBP the heritability remained unchanged at higher BMI levels. Our results suggest that higher BMIs may reduce SBP heritability through a larger impact of environmental effects. These conclusions may be valuable for gene-finding studies.

The Chinese National Twin Registry: an update.

The Chinese National Twin Registry (CNTR), established in 2001, is the first and largest population-based twin registry in China. Based on the CNTR, a new twin cohort was recruited from 2011 to study the relationship between environmental risk factors and chronic diseases. So far, 33,874 twin pairs from nine provinces have been recruited, in which hundreds of disease-discordant twin pairs and even thousands of exposure-discordant twin pairs were found in this cohort. The updates of the CNTR will be introduced in detail in this article.

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.

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.

The genetic correlation between cigarette smoking and alcohol drinking among Chinese adult male twins: An ordinal bivariate genetic analysis

BACKGROUND Though multiple policies have been implemented, the cigarette control in China is still facing a great challenge. At the same time, alcohol drinking has increasingly become a public health problem. Considering cigarette smoking and alcohol drinking often co-occur, a few studies tested the covariance of these phenotypes. However, the genetic and environmental correlation between them among Chinese population has not been determined. The main aim of this study is to fill this gap. METHODS From the Chinese National Twin Registry, we obtained the data on cigarette smoking and alcohol drinking behaviors. The ordinal bivariate genetic analysis was performed to fit the categorical variables. After identifying the best decomposition among the Cholesky, common, and independent pathway model, we established the most parsimonious submodel. RESULTS The correlation between current tobacco and alcohol use could be explained by Cholesky model. The shared environmental variances for both phenotypes were dropped to construct the most parsimonious submodel. Furthermore, the most parsimonious submodel showed a moderate correlation (0.32, 95%CI=0.17-0.46) between the genetic components and a negligible non-shared environmental correlation. CONCLUSION As the first bivariate genetic analysis on current tobacco smoking and current alcohol drinking in China, this study suggested a common genetic vulnerability to tobacco and alcohol use in male twins. Further studies should be carried out to track the pertinent genes that are related to the comorbidity of smoking and drinking in Chinese population. Another urgent need is to recognize the behavior-specific environmental risk factors.

Methylation loci associated with body mass index, waist circumference, and waist-to-hip ratio in Chinese adults: an epigenome-wide analysis

BACKGROUND DNA methylation has been implicated in the pathology of obesity, but little is known about such epigenetic variants in Chinese people. We conducted an epigenome-wide analysis of methylation at CpG sites in relation to body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) among Chinese adult populations. METHODS 469 twins from the Chinese National Twin Registry were the discovery cohort. After quality control, methylation levels in whole blood leukocyte DNA were tested for association with BMI, WC, and WHR using mixed linear regressions, adjusting for demographics, lifestyle, and family structure. Methylation sites at a false discovery rate (FDR) q value of 0·05 or less were selected for replication in four independent panels of general populations: Dongfeng-tongji cohort (n=688), Coke Oven Workers (n=137), Wuhan-Zhuhai cohort (n=241), and Shiyan participants (n=144). Association of obesity traits with the selected CpG sites in each replication panel was examined using linear regressions with adjustment of covariates similar to that in the discovery cohort, and results were combined using fixed effect meta-analysis with significance level penalised by Bonferroni correction. All participants gave written informed consent, and the Peking University Biomedical Ethics Committee approved the study protocol. FINDINGS Methylation levels at 6, 3, and 1 CpG sites were significantly associated with BMI, WC, and WHR, respectively in discovery cohort (FDR q value range 0·0010-0·0443); these findings were replicated by meta-analysis in the four panels. We found associations between obesity traits and methylation at genes CPT1A (meta-analysis p=0·0013 for BMI, p=0·0047 for WC, and p=0·0178 for WHR), ABCG1 (p<0·0001 for BMI and WC) and SREBF1 (p<0·0001 for BMI). Additionally, CpG sites at gene ARID1B (meta-analysis effect size β -0·0221, 95% CI -0·0363 to -0·0079, p=0·0022 for BMI), gene TOP1 (-0·0237, -0·0404 to -0·0071, p=0·0053 for BMI), and methylation site cg17061862 (-0·0379, -0·0575 to -0·018, p=0·0002 for BMI; -0·0356, -0·0608 to -0·0103, p=0·0057 for WC) showed inverse associations with BMI or WC. INTERPRETATION Our findings support the association of DNA methylation at CPT1A, ABCG1, and SREBF1 with obesity traits in Chinese populations. We identified additional associated methylation sites at genes ARID1B and TOP1 and at cg17061862. FUNDING This study was supported by the Specific Research Project of Health Public Service, Ministry of Health, China (201002007, 201502006) and Key Grant Project of Chinese Ministry of Education (310006).

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.

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

This study aimed to examine the gene–environment interaction of physical activity and body mass index (BMI) using the Chinese National Twin Registry (CNTR).

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.

City Level of Income and Urbanization and Availability of Food Stores and Food Service Places in China

Objective The contribution of unhealthy dietary patterns to the epidemic of obesity has been well recognized. Differences in availability of foods may have an important influence on individual eating behaviors and health disparities. This study examined the availability of food stores and food service places by city characteristics on city level of income and urbanization. Methods The cross-sectional survey was comprised of two parts: (1) an on-site observation to measure availability of food stores and food service places in 12 cities of China; (2) an in-store survey to determine the presence of fresh/frozen vegetables or fruits in all food stores. Trained investigators walked all the streets/roads within study tracts to identify all the food outlets. An observational survey questionnaire was used in all food stores to determine the presence of fresh/frozen vegetables or fruits. Urbanization index was determined for each city using a principal components factor analysis. City level of income and urbanization and numbers of each type of food stores and food service places were examined using negative binomial regression models. Results Large-sized supermarkets and specialty retailers had higher number of fresh/frozen vegetables or fruits sold compared to small/medium-sized markets. High-income versus low-income, high urbanized versus low urbanized areas had significantly more large-sized supermarkets and fewer small/medium-sized markets. In terms of restaurants, high urbanized cities had more western fast food restaurants and no statistically significant difference in the relative availability of any type of restaurants was found between high- and low-income areas. Conclusions The findings suggested food environment disparities did exist in different cities of China.