Co-methylation analyses identify CpGs associated with lipid traits in Chinese discordant monozygotic twins.

To control genetic background and early life milieu in genome-wide DNA methylation analysis for blood lipids, we recruited Chinese discordant monozygotic twins to explore the relationships between DNA methylations and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). 132 monozygotic (MZ) twins were included with discordant lipid levels and completed data. A linear mixed model was conducted in Epigenome-wide association study (EWAS). Generalized estimating equation model was for gene expression analysis. We conducted Weighted correlation network analysis (WGCNA) to build co-methylated interconnected network. Additional Qingdao citizens were recruited for validation. Inference about Causation through Examination of Familial Confounding (ICE FALCON) was used to infer the possible direction of these relationships. A total of 476 top CpGs reached suggestively significant level (P < 10-4), of which, 192 CpGs were significantly associated with TG (FDR < 0.05). They were used to build interconnected network and highlight crucial genes from WGCNA. Finally, four CpGs in GATA4 were validated as risk factors for TC; six CpGs at ITFG2-AS1 were negatively associated with TG; two CpGs in PLXND1 played protective roles in HDL-C. ICE FALCON indicated abnormal TC was regarded as the consequence of DNA methylation in CpGs at GATA4, rather than vice versa. Four CpGs in ITFG2-AS1 were both causes and consequences of modified TG levels. Our results indicated that DNA methylation levels of 12 CpGs in GATA4, ITFG2-AS1, and PLXND1 were relevant to TC, TG, and HDL-C, respectively, which might provide new epigenetic insights into potential clinical treatment of dyslipidemia.

An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

OBJECTIVES: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. METHODS: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. RESULTS: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. CONCLUSIONS: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

Mediation role of DNA methylation in association between handgrip strength and cognitive function in monozygotic twins.

Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediation analysis. In order to do an ontology enrichment study for CpGs, the GREAT program was used. There was a significant positive association between handgrip strength and cognitive function (ß = 0.194, P < 0.001). The association between handgrip strength and DNAm of 124 CpGs was found to be statistically significant at a significance level of P < 1 × 10-4. Fifteen differentially methylated regions (DMRs) related to handgrip strength were found in genes such as SNTG2, KLB, CDH11, and PANX2. Of the 124 CpGs, 4 within KRBA1, and TRAK1 mediated the association between handgrip strength and cognitive function: each 1 kg increase in handgrip strength was associated with a potential decrease of 0.050 points in cognitive function scores, mediated by modifications in DNAm. The parallel mediating effect of these 4 CpGs was -0.081. The presence of DNAm variation associated with handgrip strength may play a mediated role in the association between handgrip strength and cognitive function.

Genome-wide DNA methylation analysis of body composition in Chinese monozygotic twins.

BACKGROUND: Little is currently known about epigenetic alterations associated with body composition in obesity. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and three common traits of body composition as measured by body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) among Chinese monozygotic twins. METHODS: Generalized estimated equation model was used to regress the methylation level of CpG sites on body composition. Inference about Causation Through Examination Of Familial Confounding was used to explore the evidence of a causal relationship. Gene expression analysis was further performed to validate the results of differentially methylated genes. RESULTS: We identified 32, 22 and 28 differentially methylated CpG sites (p < 10-5 ) as well as 20, 17 and eight differentially methylated regions (slk-corrected p < 0.05) significantly associated with BF%, FM and LBM which were annotated to 65 genes, showing partially overlapping. Causal inference demonstrated bidirectional causality between DNA methylation and body composition (p < 0.05). Gene expression analysis revealed significant correlations between expression levels of five differentially methylated genes and body composition (p < 0.05). CONCLUSIONS: These DNA methylation signatures will contribute to increased knowledge about the epigenetic basis of body composition and provide new strategies for early prevention and treatment of obesity and its related diseases.

Family history, waist circumference and risk of ischemic stroke: A prospective cohort study among Chinese adults.

BACKGROUND AND AIMS: The associations between genetic factors and waist circumference (WC) with stroke risk have been evaluated in Western studies. However, evidence of this association has rarely been reported in the Chinese population. This study aimed to evaluate the association between WC and family history of stroke (FHS) with ischemic stroke (IS) risk among Chinese adults and to further explore the potential interaction of these associations. METHODS AND RESULTS: The China Kadoorie Biobank (CKB) study recruited 35,508 participants aged 30-79 years from the Qingdao urban area during 2004-2008. A total of 33,355 participants were included in study. Cox regression analysis was used to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the independent and interactional associations between FHS and WC and IS risk. Participants with FHS had a 29% (HR = 1.29, 95% CI: 1.12-1.50) higher IS risk than those without FHS. Participants with excessive WC (85 cm for males and 80 cm for females) had a 78% (HR = 1.78, 95% CI: 1.51-2.10) higher IS risk than those with normal WC. The combined effect of FHS and excessive WC on IS was statistically significant (HR = 2.29, 95% CI: 1.84-2.86). The present study further found statistically significant multiplicative interactions of FHS and WC with IS risk (Pinteraction < 0.001). CONCLUSION: The present study indicated that FHS and WC were significantly associated with an increased risk of IS. The association between FHS and IS was associated with excessive WC.

Genetic and Environmental Correlation Analysis of Serum Creatinine Levels in Chinese Twins.

Almost all creatinine is excreted by the kidney in individuals. Serum creatinine concentration, a widely used renal function index in clinical practice, can be affected by both genetic and environmental factors, as evidenced by current research exploring the relationship between these factors and kidney function. However, few studies have explored the heritability of serum creatinine in Asian populations. Therefore, we explored the genetic and environmental factors that affect the serum creatinine level in Asian populations. Participants in this study came from the Qingdao Twin Registry in China, and 374 pairs of twins were included, of which 139 pairs were dizygotic twins, whose ages ranged from 40 to 80 years old, and the serum creatinine level ranged from 10 to 126 µmol/L. Structural equation models were constructed using Mx software to calculate heritability, with adjusted covariates being age, sex, and body mass index. The results of heritability analysis showed that ACE was the best fit model. Serum creatinine level is influenced by genetic and environmental factors. The result of heritability was 35.44%, and the influence of shared environmental factors accounted for 52.13%. This study provided the relevant basis for future research on genetic and environmental factors affecting serum creatinine levels in Asian populations.

Genetic and Environmental Influences on Serum Alanine Aminotransferase Level: A Chinese Twin Study.

An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT levels have been well studied for the populations in the different countries, and the results showed moderate-to-high heritability. However, the heritability of ALT level has not been explored in Chinese population. Thus, we recruited 369 pairs of twins (233 monozygotic and 136 dizygotic) from the Qingdao Twin Registry in China with a median age of 50 years (40-80 years). Correlation analysis and a structural equation model (SEM) were conducted to evaluate the heritability of ALT level. The data for age, gender, body mass index and alcohol consumption were set as covariates. Intrapair correlation in monozygotic twins was 0.64 (95%CI [.56, .71]) and 0.42 (95% CI [.28, .55]) in dizygotic twins. The SEM analysis indicated that 65% (95% CI [57%, 71%]) of the variation in ALT levels can be explained by additive genetics and 35% (95% CI [29%, 44%]) of the variation is attributed to unique environmental factors or residuals. Shared environmental influences were not significant. In conclusion, serum ALT variations exhibited strong genetic effects. The variation could also be explained by unique environmental factors. However, shared environmental factors have a minor impact on the serum ALT level.

Estimating future PM2.5-attributed acute myocardial infarction incident cases under climate mitigation and population change scenarios in Shandong Province, China.

BACKGROUND: The effects of fine particulate matter (PM2.5) on acute myocardial infarction (AMI) have been widely recognized. However, no studies have comprehensively evaluated future PM2.5-attributed AMI burdens under different climate mitigation and population change scenarios. We aimed to quantify the PM2.5-AMI association and estimate the future change in PM2.5-attributed AMI incident cases under six integrated scenarios in 2030 and 2060 in Shandong Province, China. METHODS: Daily AMI incident cases and air pollutant data were collected from 136 districts/counties in Shandong Province from 2017 - 2019. A two-stage analysis with a distributed lag nonlinear model was conducted to quantify the baseline PM2.5-AMI association. The future change in PM2.5-attributed AMI incident cases was estimated by combining the fitted PM2.5-AMI association with the projected daily PM2.5 concentrations under six integrated scenarios. We further analyzed the factors driving changes in PM2.5-related AMI incidence using a decomposition method. RESULTS: Each 10 µg/m3 increase in PM2.5 exposure at lag05 was related to an excess risk of 1.3 % (95 % confidence intervals: 0.9 %, 1.7 %) for AMI incidence from 2017 - 2019 in Shandong Province. The estimated total PM2.5-attributed AMI incident cases would increase by 10.9-125.9 % and 6.4-244.6 % under Scenarios 1 - 3 in 2030 and 2060, whereas they would decrease by 0.9-5.2 % and 33.0-46.2 % under Scenarios 5 - 6 in 2030 and 2060, respectively. Furthermore, the percentage increases in PM2.5-attributed female cases (2030: -0.3 % to 135.1 %; 2060: -33.2 % to 321.5 %) and aging cases (2030: 15.2-171.8 %; 2060: -21.5 % to 394.2 %) would wholly exceed those in male cases (2030: -1.8 % to 133.2 %; 2060: -41.1 % to 264.3 %) and non-aging cases (2030: -41.0 % to 45.7 %; 2060: -89.5 % to -17.0 %) under six scenarios in 2030 and 2060. Population aging is the main driver of increased PM2.5-related AMI incidence under Scenarios 1 - 3 in 2030 and 2060, while improved air quality can offset these negative effects of population aging under the implementation of the carbon neutrality and 1.5 °C targets. CONCLUSION: The combination of ambitious climate policies (i.e., 1.5 °C warming limits and carbon neutrality targets) with stringent clean air policies is necessary to reduce the health impacts of air pollution in Shandong Province, China, regardless of population aging.

Genome-wide DNA methylation analysis of pulmonary function in middle and old-aged Chinese monozygotic twins.

BACKGROUND: Previous studies have determined the epigenetic association between DNA methylation and pulmonary function among various ethnics, whereas this association is largely unknown in Chinese adults. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and pulmonary function among middle-aged Chinese monozygotic twins. METHODS: The monozygotic twin sample was drawn from the Qingdao Twin Registry. Pulmonary function was measured by three parameters including forced expiratory volume the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear mixed effect model was used to regress the methylation level of CpG sites on pulmonary function. After that, we applied Genomic Regions Enrichment of Annotations Tool (GREAT) to predict the genomic regions enrichment, and used comb-p python library to detect differentially methylated regions (DMRs). Gene expression analysis was conducted to validate the results of differentially methylated analyses. RESULTS: We identified 112 CpG sites with the level of P < 1 × 10-4 which were annotated to 40 genes. We identified 12 common enriched pathways of three pulmonary function parameters. We detected 39 DMRs located at 23 genes, of which PRDM1 was related to decreased pulmonary function, and MPL, LTB4R2, and EPHB3 were related to increased pulmonary function. The gene expression analyses validated DIP2C, ASB2, SLC6A5, and GAS6 related to decreased pulmonary function. CONCLUSION: Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on pulmonary function. Several CpG sites, genes, biological pathways and DMRs are considered as possible crucial to pulmonary function.

Heritability and genome-wide association analyses of fasting plasma glucose in Chinese adult twins.

BACKGROUND: Currently, diabetes has become one of the leading causes of death worldwide. Fasting plasma glucose (FPG) levels that are higher than optimal, even if below the diagnostic threshold of diabetes, can also lead to increased morbidity and mortality. Here we intend to study the magnitude of the genetic influence on FPG variation by conducting structural equation modelling analysis and to further identify specific genetic variants potentially related to FPG levels by performing a genome-wide association study (GWAS) in Chinese twins. RESULTS: The final sample included 382 twin pairs: 139 dizygotic (DZ) pairs and 243 monozygotic (MZ) pairs. The DZ twin correlation for the FPG level (rDZ = 0.20, 95% CI: 0.04-0.36) was much lower than half that of the MZ twin correlation (rMZ = 0.68, 95% CI: 0.62-0.74). For the variation in FPG level, the AE model was the better fitting model, with additive genetic parameters (A) accounting for 67.66% (95% CI: 60.50-73.62%) and unique environmental or residual parameters (E) accounting for 32.34% (95% CI: 26.38-39.55%), respectively. In the GWAS, although no genetic variants reached the genome-wide significance level (P < 5 × 10- 8), 28 SNPs exceeded the level of a suggestive association (P < 1 × 10- 5). One promising genetic region (2q33.1) around rs10931893 (P = 1.53 × 10- 7) was found. After imputing untyped SNPs, we found that rs60106404 (P = 2.38 × 10- 8) located at SPATS2L reached the genome-wide significance level, and 216 SNPs exceeded the level of a suggestive association. We found 1007 genes nominally associated with the FPG level (P < 0.05), including SPATS2L, KCNK5, ADCY5, PCSK1, PTPRA, and SLC26A11. Moreover, C1orf74 (P = 0.014) and SLC26A11 (P = 0.021) were differentially expressed between patients with impaired fasting glucose and healthy controls. Some important enriched biological pathways, such as ß-alanine metabolism, regulation of insulin secretion, glucagon signaling in metabolic regulation, IL-1 receptor pathway, signaling by platelet derived growth factor, cysteine and methionine metabolism pathway, were identified. CONCLUSIONS: The FPG level is highly heritable in the Chinese population, and genetic variants are significantly involved in regulatory domains, functional genes and biological pathways that mediate FPG levels. This study provides important clues for further elucidating the molecular mechanism of glucose homeostasis and discovering new diagnostic biomarkers and therapeutic targets for diabetes.

The Genetic Architecture of the Clustering of Cardiometabolic Risk Factors: A Study of 8- to 17-Year-Old Chinese Twins.

We explored the genetic architecture of metabolic risk factors of cardiovascular diseases (CVDs) and their clustering in Chinese boys and girls. Seven metabolic traits (body mass index [BMI], waist circumference [WC], systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol [TC], triglyceride [TG], and uric acid [UA]) were measured in a sample of 1016 twins between 8 and 17 years of age, recruited from the Qingdao Twin Registry. Cholesky, independent pathway, and common pathway models were used to identify the latent genetic structure behind the clustering of these metabolic traits. Genetic architecture of these metabolic traits was largely similar in boys and girls. The highest heritability was found for BMI (a2 = 0.63) in boys and TC (a2 = .69) in girls. Three heritable factors, adiposity (BMI and WC), blood pressure (SBP and DBP), and metabolite factors (TC, TG, and UA), which formed one higher-order latent phenotype, were identified. Latent genetic, common environmental, and unique environmental factors indirectly impacted the three factors through one single latent factor. Our results suggest that there is one latent factor influencing several metabolic traits, which are known risk factors of CVDs in young Chinese twins. Latent genetic, common environmental, and unique environmental factors indirectly imposed on them. These results inform strategies for gene pleiotropic discovery and intervening of CVD risk factors during childhood and adolescence.

Heritability of Age-Related Hearing Loss in Middle-Aged and Elderly Chinese: A Population-Based Twin Study.

OBJECTIVES: The heritability of age-related hearing loss has been studied mostly in developed countries. The authors aimed to estimate the heritability of better ear hearing level (BEHL), defined as hearing level of the better ear at a given frequency, and pure-tone averages at the middle (0.5, 1.0, and 2.0 kHz) and high (4.0, 8.0, and 12.5 kHz) frequencies among middle-aged and elderly Chinese twins, and to explore their genetic correlations. DESIGN: This population-based twin study included 226 monozygotic and 132 dizygotic twin-pairs and 1 triplet (age range, 33 to 80 years; mean age, 51.55 years). Pure-tone air-conducted hearing thresholds in each ear were measured at the frequencies of 0.5, 1.0, 2.0, 4.0, 8.0, and 12.5 kHz with a diagnostic audiometer. Univariate and multivariate twin models were fitted to evaluate heritability and genetic correlations. RESULTS: Our data showed a reverse J-shaped pattern of BEHLs at six frequencies by age and sex. Univariate analysis showed that the heritability of BEHLs at the frequencies between 2.0 and 12.5 kHz ranged from 47.08 to 54.20%, but the heritability at the frequencies of 0.5 and 1.0 kHz was 1.65% and 18.68%, respectively. The heritability of pure-tone average at the middle and high frequencies was 34.77% and 43.26%, respectively. Multivariate analysis showed significant genetic correlations among BEHLs at all six frequencies, with the correlation coefficients ranging from 0.48 to 0.83 at middle frequencies, and from 0.46 to 0.75 at high frequencies. CONCLUSIONS: This population-based twin study suggests that genetic factors are associated with age-related hearing loss at middle and high frequencies among middle-aged and elderly Chinese.

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed. CONCLUSION: We identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired.

Genetic and Environmental Influences on Correlations Between Hearing and Cognitive Functions in Middle and Older Chinese Twins.

The genetic and environmental impacts on correlations between hearing and cognitive functions have not been well studied. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Hearing function was assessed by audiometric pure-tone hearing thresholds at different frequencies, including 0.5 kHz, 1 kHz, 2 kHz, 4 kHz, 8 kHz, and 12.5 kHz, with the lower hearing thresholds indicating better hearing function. Cognitive and hearing functions were measured on 379 complete twin pairs (240 monozygotic and 139 dizygotic pairs) with a median age of 50 years (range: 40-80 years). Bivariate twin models were fitted to quantify the genetic and environmental components of the correlations between hearing and cognitive functions. The analysis showed significantly high genetic correlation between 2 kHz of hearing and cognition (r G = -1.00, 95% CI [-1.00, -0.46]) and moderate genetic correlation between 4 kHz of hearing and cognition (r G = -0.62, 95% CI [-1.00, -0.14]). We found no significant genetic correlations between low as well as high frequencies of hearing and cognition. Low to moderate common and unique environmental correlations were shown between low frequencies of hearing and cognition (-0.13 to -0.39) and the common environmental correlation between 8 kHz, one of the high frequencies of hearing, and cognition (-0.22). The middle frequencies of hearing and cognitive functions may have a shared genetic basis. Low frequencies of hearing and cognition may share similar common and unique environmental factors. At 8 kHz, the high frequency of hearing and cognition may share similar common environment. This twin study detected a significant genetic and environmental basis in the phenotype correlation between cognition and hearing, which differed across frequencies.

Genetic and Environmental Influences on Pulmonary Function and Muscle Strength: The Chinese Twin Study of Aging.

Genetic and environmental influences on predictors of decline in daily functioning, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), handgrip, and five-times-sit-to-stand test (FTSST), have not been addressed in the aging Chinese population. We performed classical twin modeling on FEV1, FVC, handgrip, and FTSST in 379 twin pairs (240 MZ and 139 DZ) with median age of 50 years (40-80 years). Data were analyzed by fitting univariate and bivariate twin models to estimate the genetic and environmental influences on these measures of physical function. Heritability was moderate for FEV1, handgrip, and FTSST (55-60%) but insignificant for FVC. Only FVC showed moderate control, with shared environmental factors accounting for about 50% of the total variance. In contrast, all measures of pulmonary function and muscle strength showed modest influences from the unique environment (40-50%). Bivariate analysis showed highly positive genetic correlations between FEV1 and FVC (r G = 1.00), and moderately negative genetic correlations between FTSST and FEV1 (r G = -0.33) and FVC (r G = -0.42). FEV1 and FVC, as well as FEV1 and handgrip, displayed high common environmental correlations (r C = 1.00), and there were moderate correlations between FVC and handgrip (r C = 0.44). FEV1 and FVC showed high unique environmental correlations (r E = 0.76) and low correlations between handgrip and FEV1 (r E = 0.17), FVC (r E = 0.14), and FTSST (r E = -0.13) with positive or negative direction. We conclude that genetic factors contribute significantly to the individual differences in common indicators of daily functioning (FEV1, handgrip, and FTSST). FEV1 and FVC were genetically and environmentally correlated. Pulmonary function and FTSST may share similar sets of genes but in the negative direction. Pulmonary function and muscle strength may have a shared environmental background.

Associations between psychological characteristics and indicators of metabolic syndrome among Chinese adults.

Current knowledge about the relationship between psychological characteristics and metabolic syndrome (MetS) components is limited in Asian populations. The purpose of this study is to investigate linkages between physiological markers of MetS and life satisfaction, hostility, and depression in Chinese adults. Secondary analyses were conducted using cross-sectional data from parents of randomly selected middle school students participating in a pilot study in Qingdao, China. Among 440 parents who consented to participate (237 women, 203 men), 368 provided valid responses in all three categories of psychological characteristics, and only those subjects were included in these analyses. General linear models and logistic regressions were run separately by gender, controlling for covariates. Among women, life satisfaction was inversely associated with triglyceride levels (p = .04), LDL-C (p < .01), risk of hypertriglyceridemia (OR[.53], p < .01), HDL-C (OR[.78], p = .03), and MetS (OR[.52], p = .03). No associations were found between life satisfaction and any psychological characteristics among men. Among women, hostility was positively associated with triglyceride level (p = .04) and risk of hypertriglyceridemia (OR[2.12], p < .05). Among men, hostility was positively associated with waist circumference (p = .04), waist-hip ratio (p < .05), and fasting plasma insulin (p < .01). Depression was not associated with any physiological measurement in either gender. These findings indicate that relationships exist between certain psychological characteristics and physiological indicators of MetS among Chinese adults, although there may be important differences between genders.

Gene, environment and cognitive function: a Chinese twin ageing study.

BACKGROUND: the genetic and environmental contributions to cognitive function in the old people have been well addressed for the Western populations using twin modelling showing moderate to high heritability. No similar study has been conducted in the world largest and rapidly ageing Chinese population living under distinct environmental condition as the Western populations. OBJECTIVE: this study aims to explore the genetic and environmental impact on normal cognitive ageing in the Chinese twins. DESIGN/SETTING: cognitive function was measured on 384 complete twin pairs with median age of 50 years for seven cognitive measurements including visuospatial, linguistic skills, naming, memory, attention, abstraction and orientation abilities. Data were analysed by fitting univariate and bivariate twin models to estimate the genetic and environmental components in the variance and co-variance of the cognitive assessments. RESULTS: intra-pair correlation on cognitive measurements was low to moderate in monozygotic twins (0.23-0.41, overall 0.42) and low in dizygotic twins (0.05-0.30, overall 0.31) with the former higher than the latter for each item. Estimate for heritability was moderate for overall cognitive function (0.44, 95% CI: 0.34-0.53) and low to moderate for visuospatial, naming, attention and orientation abilities ranging from 0.28 to 0.38. No genetic contribution was estimated to linguistic skill, abstraction and memory which instead were under low to moderate control by shared environmental factors accounting for 23-33% of the total variances. In contrast, all cognitive performances showed moderate to high influences by the unique environmental factors. CONCLUSIONS: genetic factor and common family environment have a limited contribution to cognitive function in the Chinese adults. Individual unique environment is likely to play a major role in determining the levels of cognitive performance.

The genetic basis for cognitive ability, memory, and depression symptomatology in middle-aged and elderly chinese twins.

The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.

Distribution and diversity of hepatitis B virus genotypes in Yunnan, China.

Hepatitis B virus (HBV) is one of the most prevalent pathogens in the world, and infection with this virus is a serious threat for public health. Yunnan is considered as an important endemic center for blood-borne viruses such as human immunodeficiency virus and hepatitis C virus, in China. However, the distribution and diversity of HBV subgenotypes remain unclear in Yunnan province. In the current study, HBV positive samples were collected from different prefectures of Yunnan province and their molecular epidemiological characters were determined. Phylogenetic analysis on the pre-S/S gene (865 bps) showed the prevalence of four HBV genotypes, including genotype B (24 cases, 33.3%), genotype C (45 cases, 62.5%), genotype I (two cases, 2.78%) and C/D recombinants (one case, 1.39%). The most prevalent genotypes B and C could be sub classified into subgenotype B2 and C1, C2, C5, and C7, respectively. Clusters of subgenotype B2 and C2 consisted of strains from China and other East Asian countries, while subgenotype C1, C5, and C7 and genotype I formed a cluster together with strains from Southeast Asia. Using Bayesian inference from phylogenetic, HBV genotypes B and C were estimated to have originated in 1860s and 1910s with an evolutionary rate of 3.26 and 8.01 × 10(-4) substitutions/site/year, respectively. These findings indicate that the distribution of HBV genotypes in Yunnan was influenced by strains from the rest of China and the neighboring countries.

Genetic and environmental influences on cardiovascular disease risk factors: a study of Chinese twin children and adolescents.

We evaluated the genetic and environmental contributions to metabolic cardiovascular risk factors and their mutual associations. Eight metabolic factors (body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, total serum cholesterol, serum triglycerides, and serum uric acid) were measured in 508 twin pairs aged 8-17 years from the Qingdao Twin Registry, China. Linear structural equation models were used to estimate the heritability of these traits, as well as the genetic and environmental correlations between them. Among boys, body mass index and uric acid showed consistently high heritability (0.49-0.81), whereas other traits showed moderate to high common environmental variance (0.37-0.73) in children (8-12 years) and adolescents (13-17 years) except total cholesterol. For girls, moderate to high heritability (0.39-0.75) were obtained for six metabolic traits in children, while only two traits showed high heritability and others mostly medium to large common environmental variance in adolescents. Genetic correlations between the traits were strong in both boys and girls in children (r g = 0.64-0.99 between body mass index and diastolic blood pressure; r g = 0.71-1.00 between body mass index and waist circumference), but decreased for adolescent girls (r g = 0.51 between body mass index and waist-to-hip ratio; r g = 0.55 between body mass index and uric acid; r g = 0.61 between body mass index and systolic blood pressure). The effect of genetic factors on most metabolic traits decreased from childhood to adolescence. Both common genetic and specific environmental factors influence the mutual associations among most of the metabolic traits.