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Abstract: Aim: To explore the genetic and environmental influences on cardiovascular risk factors (CVRF) and cognitive function in the world's largest and rapidly aging Chinese population. Methods: Cognitive function and CVRF, including body mass index, systolic blood pressure, diastolic blood pressure, pulse pressure, glucose, total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDLC) and low‐density lipoprotein cholesterol were measured in 379 complete twin pairs. Univariate and bivariate twin models were fitted to estimate the genetic and environmental components in the variance and covariance of CVRF and cognition. Results: Mild‐to‐high heritability was estimated for CVRF and cognition (0.27–0.74). Unique environmental factors showed low‐to‐moderate contributions (0.23–0.56). Only HDLC presented significant common environmental contribution (0.50). Bivariate analysis showed significantly negative genetic correlations (rG) between cognition and systolic blood pressure (rG = −0.56), diastolic blood pressure (rG = −0.42), pulse pressure (rG = −0.45), and positive genetic correlations between cognition and total cholesterol (rG = 0.33), triglyceride (rG = 0.23) and HDLC (rG = 0.41). HDLC and cognition presented a unique environmental correlation (rE = −0.13), but in the opposite direction. Conclusions: Cognitive function was genetically related to systolic blood pressure, diastolic blood pressure, pulse pressure, total cholesterol, triglyceride and HDLC with a negative or positive direction. Cognition and HDLC might share part of a similar unique environmental factor. Geriatr Gerontol Int 2018; 18: 352–359. [ABSTRACT FROM AUTHOR]

Objective: Despite previous investigation, uncertainty remains about the nature of the associations of major depression (MD) with type 2 diabetes mellitus (T2DM), particularly in adult Chinese, and the relevance of generalized anxiety disorder (GAD) for T2DM.Methods: Cross-sectional data from the China Kadoorie Biobank Study, a sample of approximately 500,000 adults from 10 geographically defined regions of China, were analyzed. Past year MD and GAD were assessed using the Composite International Diagnostic Inventory. T2DM was defined as either having self-reported physician diagnosis of diabetes at age 30 or later ("clinically-identified" cases) or having a non-fasting blood glucose≥11.1mmol/L or fasting blood glucose≥7.0mmol/L but no prior diagnosis of diabetes ("screen-detected" cases). Logistic regression was used to assess the relationship between MD and GAD with clinically-identified and screen-detected T2DM, adjusting for demographic characteristics and health behaviors.Results: The prevalence of T2DM was 5.3% (3.2% clinically-identified and 2.1% screen-detected). MD was significantly associated with clinically-identified T2DM (odds ratio [OR]: 1.75, 95% confidence interval (CI): 1.47-2.08), but not with screen-detected T2DM (OR: 1.18, 95% CI: 0.92-1.51). GAD was associated with clinically-identified (OR: 2.14, 95% CI: 1.60-2.88) and modestly associated with screen-detected (OR: 1.44, 95% CI: 0.99-2.08) T2DM. The relationship between MD and GAD with T2DM was moderated by obesity.Conclusion: MD is associated with clinically-identified, but not screen-detected T2DM. GAD is associated with both clinically-identified and screen-detected T2DM. The relationship between MD and T2DM is strongest among those who are not obese. [ABSTRACT FROM AUTHOR]

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers. • Women having a female co-twin have similar education than as having a male co-twin. • Men having a male co-twin have higher education than if having a female co-twin. • There is no evidence for the Twin Testosterone Transfer hypothesis for education. • Having a same-sex co-twin may help men in their educational career. [ABSTRACT FROM AUTHOR]

Dyslipidemia is one of the cardiometabolic risk factors that influences mortality globally. Unraveling the causality between blood lipids and metabolites and the complex networks connecting lipids, metabolites, and other cardiometabolic traits can help to more accurately reflect the body's metabolic disorders and even cardiometabolic diseases. We conducted targeted metabolomics of 248 metabolites in 437 twins from the Chinese National Twin Registry. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) analysis was used for causal inference between metabolites and lipid parameters. Bidirectional mediation analysis was performed to explore the linkages between blood lipids, metabolites, and other seven cardiometabolic traits. We identified 44, 1, and 31 metabolites associated with triglyceride (TG), total cholesterol (TC), and high-density lipoprotein-cholesterol (HDL-C), most of which were gut microbiota-derived metabolites. There were 9, 1, and 14 metabolites that showed novel associations with TG, TC, and HDL-C, respectively. ICE FALCON analysis found that TG and HDL-C may have a predicted causal effect on 23 and six metabolites, respectively, and one metabolite may have a predicted causal effect on TG. Mediation analysis discovered 14 linkages connecting blood lipids, metabolites, and other cardiometabolic traits. Our study highlights the significance of gut microbiota-derived metabolites in lipid metabolism. Most of the identified cross-sectional associations may be due to the lipids having a predicted causal effect on metabolites, but not vice versa, nor are they due to family confounding. These findings shed new light on lipid metabolism and personalized management of cardiometabolic diseases., Competing Interests: Conflict of interest All the authors declare no conflicts of interest in this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The relationship between seafood consumption and cardiovascular disease (CVD) is controversial, and studies have not considered competing risk events. Our study examined the association between a full range of seafood consumption and CVD incidence and mortality based on the Qingdao Diabetes Prevention Program., Methods and Results: We followed up 5285 participants without CVD at baseline until December 31, 2021. CVD cases and deaths were identified through record linkage with the Qingdao CVD Surveillance System and the Qingdao Death Surveillance System, respectively. Information on seafood consumption was obtained using a food frequency questionnaire. We used the Cox proportional hazard model and the competing risk model to evaluate the association between all types of seafood consumption and CVD incidence and mortality. During a median follow-up of 11.4 years, 122 CVD cases and 75 deaths occurred. After adjustment for potential confounders, compared with nonconsumers, seafood consumption of 300-500 and > 500 g/week was associated with a lower risk of CVD incidence [hazards ratio and 95 % confidence interval (CI): 0.54 (0.29-0.99) and 0.49 (0.26-0.91), respectively]. However, seafood consumption of >500 g/week had a significantly lower risk of CVD mortality [subdistribution hazard ratio and 95 % CI: 0.40 (0.17-0.95)], but it was insignificant in other groups., Conclusion: Seafood consumption of 300-500 g/week and >500 g/week was associated with a lower CVD incidence and mortality. Our findings provide evidence of the recommendations of the 2022 Dietary Guidelines for Chinese residents and may guide the promotion of strategies for CVD prevention., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population., Methods: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately., Results: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model., Conclusions: In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background/objectives: This study examined the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood during the 1959-1961 Chinese Famine., Subjects/methods: A total of 3,418 individuals aged 35-74 years free of diabetes from two studies in 2006 and 2009 were followed up prospectively in 2009 and 2012, respectively. Famine exposure was classified as unexposed (individuals born in 1962-1978), fetal exposed (individuals born in 1959-1961), child exposed (individuals born in 1949-1958), and adolescent/adult exposed (born in 1931-1948). A logistic regression model was used to assess the relationship between famine exposure and diabetes after adjustment for potential covariates., Results: During a three-year follow-up, the age-adjusted incidence rates of type 2 diabetes were 5.7%, 14.5%, 12.7%, and 17.8% in unexposed, fetal-exposed, child-exposed, and adolescent/adult-exposed groups, respectively ( P < 0.01). Relative to the unexposed group, the relative risks (95% confidence interval) for diabetes were 2.15 (1.29-3.60), 1.53 (0.93-2.51), and 1.65 (0.75-3.63) in the fetal-exposed, child-exposed, and adolescent/adult-exposed groups, after controlling for potential covariates. The interactions between famine exposure and obesity, education level, and family history of diabetes were not observed, except for the urbanization type. Individuals living in rural areas with fetal and childhood famine exposure were at a higher risk of type 2 diabetes, with relative risks of 8.79 (1.82-42.54) and 2.33 (1.17-4.65), respectively., Conclusions: These findings indicate that famine exposure in early life is an independent predictor of type 2 diabetes, particularly in women. Early identification and intervention may help prevent diabetes in later life., Trial Registration: ClinicalTrials.gov Identifier: NCT01053195., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Background: Studies investigating the relationship between egg consumption and the risk of cerebrovascular disease (CED) have yielded inconsistent results. This study evaluated the association between egg consumption and the risk of CED among Chinese adults., Methods: Data were obtained from China Kadoorie Biobank, Qingdao. A computerised questionnaire was used to collect information regarding egg consumption frequency. CED events were tracked through linkage with the Disease Surveillance Point System and the new national health insurance databases. Cox proportional hazards regression analyses were used to evaluate associations between egg consumption and CED risk controlling for potential confounders., Results: After a median follow-up of 9.2 years, 865 and 1083 CED events among men and women, respectively, were documented. More than 50% of participants consumed eggs daily with an average age of 52.0 (10.4) years at baseline. No association between egg consumption and CED were identified in the whole cohort and women. However, a 28% lower risk of CED was observed in those who consumed eggs at a higher frequency (HR = 0.72, 95% CI: 0.55-0.95) and a significant trend for the association ( p for trend = 0.012) in a multivariable model in men., Conclusion: Higher frequency of egg consumption was associated with a lower risk of total CED events among men but not women in Chinese adults. The beneficial effect on women warrants further investigations.

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 (P interaction < 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., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Previous EWASs (Epigenome-Wide Association Studies) have reported hundreds of blood pressure (BP) associated 5'-cytosine-phosphate-guanine-3' (CpG) sites. However, their results were inconsistent. Longitudinal observations on the temporal relationship between DNA methylation and BP are lacking., Methods: A candidate CpG site association study for BP was conducted on 1072 twins in the Chinese National Twin Registry. PubMed and EMBASE were searched for candidate CpG sites. Cross-lagged models were used to assess the temporal relationship between BP and DNA methylation in 308 twins who completed 2 surveys in 2013 and 2018. Then, the significant cross-lagged associations were validated by adopting the Inference About Causation From Examination of Familial Confounding approach. Finally, to evaluate the cumulative effects of DNA methylation on the progression of hypertension, we established methylation risk scores based on BP-associated CpG sites and performed Markov multistate models., Results: 16 and 20 CpG sites were validated to be associated with systolic BP and diastolic BP, respectively. In the cross-lagged analysis, we detected that methylation of 2 CpG sites could predict subsequent systolic BP, and systolic BP predicted methylation at another 3 CpG sites. For diastolic BP, methylation at 3 CpG sites had significant cross-lagged effects for predicting diastolic BP levels, while the prediction from the opposite direction was observed at one site. Among these, 3 associations were validated in the Inference About Causation From Examination of Familial Confounding analysis. Using the Markov multistate model, we observed that methylation risk scores were associated with the development of hypertension., Conclusions: Our findings suggest the significance of DNA methylation in the development of hypertension.

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.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations., (© 2022. The Author(s).)

Objective: This study aimed to examine the association of socioeconomic status with obesity., Methods: A total of 39,262 twin individuals were included from the Chinese National Twin Registry (CNTR). Generalized estimating equation models for unmatched twin individual analyses and conditional logistic regression for the co-twin matched design were used. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was used to explore the evidence of a causal relationship., Results: In general estimating equation models, high education level and income were associated with lower risk of obesity (odds ratio [OR] = 0.74 [95% CI: 0.65 to 0.84] and 0.86 [95% CI: 0.77 to 0.96]). In conditional logistic regression analysis, the association with education was significant (OR = 0.50 [95% CI: 0.34 to 0.74]) but the association with income was insignificant (OR = 0.74 [95% CI: 0.48 to 1.15]). From the ICE FALCON analysis, a twin's obesity was associated with the co-twin's education and income. After adjusting for the twin's own education, the association disappeared ( β co - twin '  = -0.10 [95% CI: -0.26 to 0.07]), whereas the twin's obesity was still associated with the co-twin's income but attenuated toward the null ( β co - twin '  = -0.21 [95% CI: -0.36 to -0.06])., Conclusions: Socioeconomic status is negatively associated with obesity. Education may have a causal effect on obesity, whereas the association between income and obesity is confounded by familial factors., (© 2022 The Obesity Society.)

Aims/hypothesis: We aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association., Methods: This prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association via co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated., Results: Overall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant ( P =0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them ( r A = 0.59, 95% CI: 0.44~1.00)., Conclusions/interpretation: Genetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XT declared a shared affiliation, with no collaboration, with ZP to the handling editor at the time of review., (Copyright © 2021 Xi, Gao, Zheng, Lv, Yu, Wang, Huang, Sun, Liao, Pang, Pang, Yu, Wang, Wu, Dong, Wu, Jiang, Wang, Liu, Deng, Lu, Cao and Li.)

We investigated whether lifestyle influences epigenetic aging in 143 monozygotic twin pairs discordant for the combined healthy lifestyle score. Twins were scored for four lifestyle factors as unhealthy or healthy; non-smoker, moderate drinker, adequate fruit and vegetable intake, and sufficient physical activity. The combined healthy lifestyle score was calculated for each participant by summing the binary score for each factor. Individual and co-twin analyses were used to assess the relationship between single or combined lifestyle scores, along with DNA methylation age acceleration (AA) calculated using Horvath's and Li's epigenetic clocks, focusing on AA and intrinsic epigenetic age acceleration (IEAA) measures. Compared with the twins that scored no or one healthy lifestyle point, those who scored four healthy lifestyle points had lower Li&#95;IEAA with similar results observed in the co-twin analysis. No significant relationships were found in analyses based on Horvath's clock, although the direction of correlations was consistent with that determined using Li's clock. Smoking and drinking did not significantly affect DNA methylation AA; however, physical activity and intake of vegetables and fruits did, although the influence varied depending on the epigenetic clock. Our findings suggest that a healthy lifestyle may be an important way to delay aging and prevent age-related diseases.

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) (β=0.42, 95% CI: 0.21-0.64), metabolically healthy obesity (MHO) (β=0.68, 95% CI: 0.36-1.00) and metabolically unhealthy obesity (MUO) (β=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., Competing Interests: The authors declare that they have no competing interests., (© 2021 Liao et al.)

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.

The default mode network (DMN) is thought to reflect endogenous neural activity, which is considered as one of the most intriguing phenomena in cognitive neuroscience. Previous studies have found that key regions within the DMN are highly interconnected. Here, we characterized the genetic influences on causal or directed information flow within the DMN during the resting state. In this study, we recruited 46 pairs of twins and collected fMRI imaging data using a 3.0 T scanner. Dynamic causal modeling was conducted for each participant, and a structural equation model was used to calculate the heritability of DMN in terms of its effective connectivity. Model comparison favored a full-connected model. Structural equal modeling was used to estimate the additive genetics (A), common environment (C) and unique environment (E) contributions to variance for the DMN effective connectivity. The ACE model was preferred in the comparison of structural equation models. Heritability of DMN effective connectivity was 0.54, suggesting that the genetic made a greater contribution to the effective connectivity within DMN. Establishing the heritability of default-mode effective connectivity endorses the use of resting-state networks as endophenotypes or intermediate phenotypes in the search for the genetic basis of psychiatric or neurological illnesses., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Multiple loci or genes have been identified using genome-wide association studies mainly in western countries but with inconsistent results. No similar studies have been conducted in the world's largest and rapidly aging Chinese population. The paper aimed to identify the specific genetic variants associated with cognitive function in middle and old-aged Chinese dizygotic twins (DZ). Cognitive function was measured on 139 pairs of DZ by Montreal Cognitive Assessment. The subjects were genotyped at 1048575 SNP positions. Regression-based mixed-effect kinship model of GWAS was conducted to test the SNPs. Gene-based analysis was performed on VEGAS2. The statistically significant genes were then subject to gene set enrichment analysis to further identify the specific biological pathways associated with cognitive function. No SNPs reached genome-wide significance although there were 13 SNPs of suggestive significance (P < 10 -5 ). Gene-based analysis found 823 significant genes topped by TNRC18P1 (P = 1.00 × 10 -6 ), FGFR1OP2 (P = 6.00 × 10 -6 ), and AKR1D1 (P = 2.30 × 10 -5 ). Enrichment analysis identified 46 biological pathways, mainly involving in signaling transmission, metabolic process and Alzheimer's disease. Analysis of SNPs involved in the regulatory motif detected cell-type specific enhancers involving aorta and colon smooth muscle both have been reported to implicate in cognition. We conclude that genetic variations are significantly involved in functional genes, biological pathways and the regulatory domain that mediate cognitive performances.

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors., Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses., Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m2 higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m2 per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood., Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood., (© The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background and Objectives: Fruit, vegetable, seafood, and dairy intake may reduce the risk of type 2 diabetes, but this relationship is unclear. We aimed to examine the associations between fruit, vegetable, seafood, and dairy intake and type 2 diabetes prevalence in a Chinese population., Methods and Study Design: A total of 4,343 individuals aged 35-74 years participated in a population-based cross-sectional study in Qingdao, China. The frequency and quantity of fruit, vegetable, seafood, and dairy intake were determined using a standard food frequency questionnaire. Diabetes was classified according to the WHO/IDF 2006 criteria. Logistic regression analysis was employed to estimate odds ratio (OR) for type 2 diabetes in relation to fruit, vegetable, seafood, and dairy intake in a multivariable model., Results: The multivariate-adjusted ORs (95% confidence interval) for the presence of type 2 diabetes were 0.68 (0.46-0.98), 0.50 (0.37-0.68), and 0.91 (0.66-1.25), respectively, for the highest versus the lowest groups regarding total fruit and vegetable, fruit or vegetable intake in women. The ORs for type 2 diabetes prevalence regarding the quantity of fruit and vegetable, fruit, and yogurt intake were 0.88 (0.78-0.99), 0.71 (0.61-0.82), and 0.56 (0.32-0.98) in women, but not in men. Seafood consumption was inversely associated with diabetes risk in men, but not in women; the corresponding figures were 0.58 (0.35-0.96) and 0.92 (0.63-1.36), respectively., Conclusions: Fruit, vegetable, and yogurt intake in women and seafood intake in men were inversely associated with type 2 diabetes prevalence in this Chinese population. These findings require confirmation in a prospective study.

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.

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 Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

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.

Objective: Since the incidence rates and risk factor for type 2 diabetes in Chinese populations had not been well known, the aim of this study was to evaluate the impact of weight change and other risk factors on incident type 2 diabetes in Qingdao, China., Methods: A prospective population-based cohort study was carried out, based on subjects aged 35-74 years who participated in the 'Qingdao Diabetes Survey' in 2006. Subjects were free of diabetes at baseline. A total of 1 294 subjects attended the follow up survey between 2009 and 2011. The diagnostic criteria for Diabetes was classified according to both the World Health Organization and the International Diabetes Federation 2006. A logistic regression was built using the backward stepwise selection to assess the effects of risk factors on the incident type 2 diabetes., Results: During a 4-year follow up period, 120 cases with incident type 2 diabetes were identified, with cumulative incidence of diabetes as 11.8% . Participants who developed type 2 diabetes were significantly older, having significantly higher age-adjusted BMI/waist circumference/systolic blood pressure and total cholesterol, than those subjects who remained non-diabetic both in urban and rural areas. Among individuals with no diabetes at the baseline, factors as age, living in the rural areas, baseline BMI and weight change had all independently contributed to the development of diabetes. The multivariate adjusted relative risks (95%CIs) related to the incidence of diabetes were 1.45 (1.13-1.87), 1.93 (1.12-3.34), 1.46 (1.05-2.03) and 1.49 (1.18-1.88), respectively, for a one standard deviation increase in continuous variables. Compared with the reference group of non-obese and with stable weight, factor as weight loss >5% and BMI <28 kg/m² were independently associated with a 67% (RR = 0.33, 95% CI: 0.11-0.97)reduction in the risk of type 2 diabetes, while BMI >28 kg/m² could increase the risk across the levels of weight change. Similar trends were observed in higher waist and weight gain at baseline., Conclusion: This study confirmed the critical importance of obesity in the development of type 2 diabetes. Baseline BMI and weight gain appeared independent predictors on type 2 diabetes.

Objective: To investigate both genetic and environmental influences on the exercise participation and sedentary behavior in Qingdao, Shandong province and 326 in Lishui, Zhejiang province., Methods: 568 twin pairs, including 242 in Qingdao and 326 in Lishui, were studied. Exercise participation was measured by two questions on the frequency and intensity and then divided into two groups. Sedentary behavior was measured by one question as 'how long do you spend on sitting every day'. Variance component models based on twins was used to estimate the genetic and environmental factors on these traits., Results: The average age in monozygotic twins was (41.14 ± 10.11)while in dizygotic twins it was (41.23 ± 9.89). Genetic factors accounted 78% (35%-96%) and 59% (0-94%) for exercise participation variance in Qingdao and Lishui in people aged between 20 and 40. However, there were no heritability noticed on physical activity in people older than 40 years of age. Rates of heritability on sedentary behavior in Qingdao and Lishui were 68% (59%-75%) and 32% (7%-62%), respectively., Conclusion: Results from the study suggested that sedentary behavior in Chinese people was influenced by genetic factors, which could also explain much of the exercise participation variance in people aged between 20 and 40.

Background: Despite the great burden of chronic respiratory diseases in China, few large multicentre, spirometry-based studies have examined its prevalence, rate of underdiagnosis regionally or the relevance of socioeconomic and lifestyle factors., Methods: We analysed data from 512 891 adults in the China Kadoorie Biobank, recruited from 10 diverse regions of China during 2004-2008. Air flow obstruction (AFO) was defined by the lower limit of normal criteria based on spirometry-measured lung function. The prevalence of AFO was analysed by region, age, socioeconomic status, body mass index (BMI) and smoking history and compared with the prevalence of self-reported physician-diagnosed chronic bronchitis or emphysema (CB/E) and its symptoms., Findings: The prevalence of AFO was 7.3% in men (range 2.5-18.2%) and 6.4% in women (1.5-18.5%). Higher prevalence of AFO was associated with older age (p<0.0001), lower income (p<0.0001), poor education (p<0.001), living in rural regions (p<0.001), those who started smoking before the age of 20 years (p<0.001) and low BMI (p<0.001). Compared with self-reported diagnosis of CB/E, 88.8% of AFO was underdiagnosed; underdiagnosis proportion was highest in 30-39-year olds (96.7%) compared with the 70+ age group (81.1%), in women (90.7%), in urban areas (89.4%), in people earning 5K-10 K ¥ monthly (90.3%) and in those with middle or high school education (92.6%)., Interpretation: In China, the burden of AFO based on spirometry was high and significantly greater than that estimated based on self-reported physician-diagnosed CB/E, especially in rural areas, reflecting major issues with diagnosis of AFO that will impact disease treatment and management.

Objective: To study the correlation between fingerprints and body size indicators in adulthood., Methods: Samples were composed of twins from two sub-registries of Chinese National Twin Registry (CNTR), including 405 twin pairs in Lishui and 427 twin pairs in Qingdao. All participants were asked to complete the field survey, consisting of questionnaire, physical examination and blood collection. From the 832 twin pairs, those with complete and clear demographic prints were selected as the target population. Information of Fingerprints pixel on the demographic characteristics of these 100 twin pairs and their related adulthood body type indicators were finally chosen to form this research. Descriptive statistics and mixed linear model were used for data analyses., Results: In the mixed linear models adjusted for age and sex, data showed that the body fat percentage of those who had arches was higher than those who did not have the arches (P = 0.002), and those who had radial loops would have higher body fat percentage when compared with ones who did not (P = 0.041). After adjusted for age, there appeared no statistically significant correlation between radial loops and systolic pressure, but the correlations of arches (P = 0.031)and radial loops (P = 0.022) to diastolic pressure still remained statistically significant., Conclusion: Statistically significant correlations were found between fingerprint types and body size indicators, and the fingerprint types showed a useful tool to explore the effects of uterine environment on health status in one's adulthood.

Objective: To develop a New Chinese Diabetes Risk Score for screening undiagnosed type 2 diabetes in China., Research Design and Methods: Data from the China National Diabetes and Metabolic Disorders Study conducted from June 2007 to May 2008 comprising 16,525 men and 25,284 women aged 20-74 years were analyzed. Undiagnosed type 2 diabetes was detected based on fasting plasma glucose ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L in people without a prior history of diabetes. β-Coefficients derived from a multiple logistic regression model predicting the presence of undiagnosed type 2 diabetes were used to calculate the New Chinese Diabetes Risk Score. The performance of the New Chinese Diabetes Risk Score was externally validated in two studies in Qingdao: one is prospective with follow-up from 2006 to 2009 (validation 1) and another cross-sectional conducted in 2009 (validation 2)., Results: The New Chinese Diabetes Risk Score includes age, sex, waist circumference, BMI, systolic blood pressure, and family history of diabetes. The score ranges from 0 to 51. The area under the receiver operating curve of the score for undiagnosed type 2 diabetes was 0.748 (0.739-0.756) in the exploratory population, 0.725 (0.683-0.767) in validation 1, and 0.702 (0.680-0.724) in validation 2. At the optimal cutoff value of 25, the sensitivity and specificity of the score for predicting undiagnosed type 2 diabetes were 92.3 and 35.5%, respectively, in validation 1 and 86.8 and 38.8% in validation 2., Conclusions: The New Chinese Diabetes Risk Score based on nonlaboratory data appears to be a reliable screening tool to detect undiagnosed type 2 diabetes in Chinese population.

Objective: To explore the synergistic effect between diabetes family history and abnormal waist-to-hip ratio (WHR) on the incidence of type 2 diabetes., Methods: Population-based case-control study was conducted. The interaction between diabetes family history and abnormal WHR was analysed by an additive model., Results: After adjusting confounding factors by multiple logistic regression analysis, the synergy index was 5.63, the attributable risk was 1.49, and the attributable interaction percent was 52.9%., Conclusion: There was a synergistic effect between diabetes family history and abnormal WHR on the incidence of type 2 diabetes.

Tobacco use among Chinese adolescents is increasing at approximately 80,000 new smokers per day. Assessing the causes for initiating tobacco use in China will be important in developing effective interventions and policies to stem rising prevalence rates. This study tested predictors of Resilience Theory in a sample of 602 Chinese adolescents. Results revealed that prior adversity, measured through school and family-related events, was significantly associated with increased smoking in females. Family factors (i.e., family cohesion, family adaptability, parental monitoring) and one personal factor (i.e., academic score) were associated with lower odds for smoking due to prior adversity and negative disposition.

Objective: To study the level and heritability of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in adult twins sampled from Qingdao City of China., Methods: 316 pairs of healthy twin aged 18 to 60 years were recruited from the database of Qingdao City twin registry. Fasting serum lipids were detected by automatic biochemical analyzer. The zygosity of twins was established by using polymorphic DNA-based microsatellite markers. The heritability was estimated by formulating univariate ACE twin mode in Mx soft., Results: The average levels of fasting serum TC, HDL-C, LDL-C and TG were (4.52 +/- 1.08), (1.46 +/- 0.39), (2.58 +/- 0.79) and (1.11 +/- 0.77) mmol/L, respectively. The best fitting models adjusted by sex and age in Mx soft were AE model for TC, HDL-C and LDL-C, whereas CE model for TG. The heritability of TC, HDL-C, LDL-C and TG were 53% , 62% , 57% and 0, respectively., Conclusion: It is considered that both genetic and environmental factors may influence the level of TC, HDL-C and LDL-C, whereas environmental effect may be the factor essential for the level of TG.