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1.  The association of cigarette smoking and alcohol drinking with body mass index: a cross-sectional, population-based study among Chinese adult male twins 
BMC Public Health  2016;16:311.
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.
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.
After adjustment for a variety of socio-demographic and lifestyle factors, former smokers had higher BMI (β = 0.475; 95 % CI, 0.196 to 0.754) whereas moderate to heavy smokers had lower BMI (β = −0.115; 95 % CI, −0.223 to −0.007) when compared with nonsmokers. BMI decreased with increased cigarette pack-years (β = −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 (β = −0.137; 95 % CI, −0.215 to −0.058), with the intake of alcohol decreasing the additive genetic component of BMI.
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.
PMCID: PMC4827244  PMID: 27068329
Twin studies; Body mass index; Gene-environment interaction; Smoking; Alcohol drinking
2.  City Level of Income and Urbanization and Availability of Food Stores and Food Service Places in China 
PLoS ONE  2016;11(3):e0148745.
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.
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.
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.
The findings suggested food environment disparities did exist in different cities of China.
PMCID: PMC4777357  PMID: 26938866
3.  Associations of Body Composition Measurements with Serum Lipid, Glucose and Insulin Profile: A Chinese Twin Study 
PLoS ONE  2015;10(11):e0140595.
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.
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.
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.
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.
PMCID: PMC4640552  PMID: 26556598
4.  Determination of Zygosity in Adult Chinese Twins Using the 450K Methylation Array versus Questionnaire Data 
PLoS ONE  2015;10(4):e0123992.
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.
PMCID: PMC4415785  PMID: 25927701
5.  Heritability of Smoking, Alcohol Use, and Psychological Characteristics Among Adolescent Twins in Qingdao, China 
Previous studies of genetic and environmental influences on adolescent substance use have been limited to Western samples.
This study assesses genetic and environmental contributions to cigarette smoking, alcohol use, and psychological variables (depression, anxiety, aggression, hostility) among 602 pairs of adolescent twins, 11 to 19 years old, in Qingdao, China.
Heritable influences were more pronounced for alcohol use than cigarette smoking. In univariate analyses, no heritable effects were found for depression or aggression, and modest heritability was found for anxiety. Hostility was relatively more heritable in girls than boys. Bivariate associations between substance use and psychological measures could be attributed to a combination of common genetic and environmental factors.
Among Chinese adolescents, experimentation with tobacco is familial, and experimentation with alcohol is heritable. The genetic and environmental architecture of hostility differs by gender. Consistency of univariate results with Western adolescent samples appears limited to the alcohol use measures.
PMCID: PMC4406051  PMID: 20484245
child health; family medicine; adolescent health; public health; smoking/tobacco/drug abuse; health informatics; health management; health education; health promotion; medical statistics
6.  Association between Ambient Temperature and Blood Pressure and Blood Pressure Regulators: 1831 Hypertensive Patients Followed Up for Three Years 
PLoS ONE  2013;8(12):e84522.
Several studies have suggested an association between ambient air temperature and blood pressure. However, this has not been reliably confirmed by longitudinal studies. Also, whether the reaction to temperature stimulation is modified by other factors such as antihypertensive medication is rarely investigated. The present study explores the relationship between ambient temperature and blood pressure, without and with antihypertensive medication, in a study of 1,831 hypertensive patients followed up for three years, in two or four weekly check ups, accumulating 62,452 follow-up records. Both baseline and follow-up blood pressure showed an inverse association with ambient temperature, which explained 32.4% and 65.6% of variation of systolic blood pressure and diastolic blood pressure (P<0.05) respectively. The amplitude of individual blood pressure fluctuation with temperature throughout a year (a 29 degrees centigrade range) was 9.4/7.3 mmHg. Medication with angiotensin converting enzyme inhibitor benazepril attenuated the blood pressure fluctuation by 2.4/1.3 mmHg each year, though the inverse association of temperature and blood pressure remained. Gender, drinking behavior and body mass index were also found to modify the association between temperature and diastolic blood pressure. The results indicate that ambient temperature may negatively regulate blood pressure. Hypertensive patients should monitor and treat blood pressure more carefully in cold days, and it could be especially important for the males, thinner people and drinkers.
PMCID: PMC3877276  PMID: 24391962
7.  Improved Doubly Robust Estimation when Data are Monotonely Coarsened, with Application to Longitudinal Studies with Dropout 
Biometrics  2010;67(2):536-545.
A routine challenge is that of making inference on parameters in a statistical model of interest from longitudinal data subject to drop out, which are a special case of the more general setting of monotonely coarsened data. Considerable recent attention has focused on doubly robust estimators, which in this context involve positing models for both the missingness (more generally, coarsening) mechanism and aspects of the distribution of the full data, that have the appealing property of yielding consistent inferences if only one of these models is correctly specified. Doubly robust estimators have been criticized for potentially disastrous performance when both of these models are even only mildly misspecified. We propose a doubly robust estimator applicable in general monotone coarsening problems that achieves comparable or improved performance relative to existing doubly robust methods, which we demonstrate via simulation studies and by application to data from an AIDS clinical trial.
PMCID: PMC3061242  PMID: 20731640
Coarsening at random; Discrete hazard; Dropout; Longitudinal data; Missing at random
8.  Improving efficiency and robustness of the doubly robust estimator for a population mean with incomplete data 
Biometrika  2009;96(3):723-734.
Considerable recent interest has focused on doubly robust estimators for a population mean response in the presence of incomplete data, which involve models for both the propensity score and the regression of outcome on covariates. The usual doubly robust estimator may yield severely biased inferences if neither of these models is correctly specified and can exhibit nonnegligible bias if the estimated propensity score is close to zero for some observations. We propose alternative doubly robust estimators that achieve comparable or improved performance relative to existing methods, even with some estimated propensity scores close to zero.
PMCID: PMC2798744  PMID: 20161511
Causal inference; Enhanced propensity score model; Missing at random; No unmeasured confounders; Outcome regression
9.  Postmarketing surveillance study of benazepril in chinese patients with hypertension: An open-label, experimental, epidemiologic study 
Benazepril hydrochloride is an angiotensin-converting enzyme inhibitor. Previous clinical trials show that antihypertensive treatment with benazepril provides effective blood pressure (BP) control and is generally well tolerated by patients with hypertension. However, the long-term antihypertensive effects and tolerability of benazepril remain to be established in Chinese patients with hypertension.
The aim of this study was to investigate the long-term efficacy and tolerability of benazepril in Chinese patients with essential hypertension.
This 36-month, community-based, open-label, postmarketing surveillance study was conducted in the Nanshi District (Shanghai, China). Chinese patients with essential hypertension were to receive 1 or more benazepril tablets PO QD in the morning for 36 months. Data for BP and pulse pressure (PP) were collected at baseline (month 0) and throughout the surveillance period. The rate of patients achieving BP targets (systolic BP [SBP]/diastolic BP [DBP], <140/<90 mm Hg) was determined, as was the rate of decrease in BP. Subanalyses by sex and age group also were conducted.
A total of 1831 patients (1090 men, 741 women; mean [SD] age, 55.8 [10.1] years [range, 35–88 years]) entered the study. After the 36-month treatment period, 75.7% of patients receiving benazepril as prescribed (1289 patients) had achieved the SBP target, 87.4% achieved the DBP target, and 71.5% achieved both targets. After 36 months of treatment, the mean (SD) decreases in SBP, DBP, and PP were 15.1 (0.4) mm Hg, 11.0 (0.3) mm Hg, and 4.2 (0.4) mm Hg, respectively, among compliers. In general, the rate of BP decrease slowed over time. No serious adverse drug reactions (ADRs) were detected during the 36-month follow-up period. All ADRs except cough (19.9%) occurred at a relatively low incidence rate (<3.0%). The cumulative incidence of benazepril related cough was statistically significantly higher in women than in men (23.6% vs 18.8%, respectively; P = 0.007). Of the 1831 patients studied, 1360 patients (74.3%) persisted in taking benazepril and were considered optimally compliant at 36-month follow-up.
In this study of Chinese patients with hypertension, benazepril was associated with prolonged, stable efficacy in lowering BP and relatively low incidence of ADRs.
PMCID: PMC3964560  PMID: 24672086

Results 1-9 (9)