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.

Association of seafood consumption with cardiovascular disease among adults in Qingdao, China.

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.

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins.

Obesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (ß = 1.86, p = .0004). The association between BMI and DNAm of 85 CpGs reached p < 1×10-4 level. Eleven BMI-related differentially methylated regions (DMRs) within LNCPRESS1, OGDHL, RNU1-44P, NPHS1, ECEL1P2, LLGL2, RNY4P15, MOGAT3, PHACTR3, and BAI2 were found. Of the 85 CpGs, 9 mapped to C10orf71-AS1, NDUFB5P1, KRT80, BAI2, ABCA2, PEX11G and FGF4 were significantly associated with SBP levels. Of the 9 CpGs, 2 within ABCA2 negatively mediated the association between BMI and SBP, with a mediating effect of -0.24 (95% CI [-0.65, -0.01]). BMI was also positively associated with DBP (ß = 0.60, p = .0495). The association between BMI and DNAm of 193 CpGs reached p < 1×10-4 level. Twenty-five BMI-related DMRs within OGDHL, POU4F2, ECEL1P2, TTC6, SMPD4, EP400, TUBA1C and AGAP2 were found. Of the 193 CpGs, 33 mapped to ABCA2, ADORA2B, CTNNBIP1, KDM4B, NAA60, RSPH6A, SLC25A19 and STIL were significantly associated with DBP levels. Of the 33 CpGs, 12 within ABCA2, SLC25A19, KDM4B, PTPRN2, DNASE1, TFCP2L1, LMNB2 and C10orf71-AS1 negatively mediated the association between BMI and DBP, with a total mediation effect of -0.66 (95% CI [-1.07, -0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

A preliminary research on transcultural capacity in global public health: from the view of public health professionals.

BACKGROUND: Transcultural capacity is a key component of consolidated global public health assistance cooperation (GPHAC). The aim of this study is to investigate the transcultural capacity perceptions of public health professionals from China's disease control and prevention system after relative training in order to provide a reference for enhancing transcultural capacity during the practice of GPHAC. METHODS: A cross sectional qualitative survey in which self-administrated questionnaire with 5 open ended questions was used. The questionnaire was disseminated on the completion of an online training for China's senior public health professions on transcultural capacity in GPHAC. Descriptive statistics, word frequency analysis and content analysis were used to analyze the questionnaire data. RESULTS: Totally, 45 participants took part in this training, 25 of them voluntarily participated in this survey. The participants demonstrated the need for transcultural competence in public health services and suggested improvement in the course content arising from their wealth of knowledge and practical experience in the field. 96% of the participants considered that the training course was "very necessary" and "meaningful". The most interested topics were "Overview of transcultural adaptation and GPHAC", "Transcultural adaptation and response" and "African culture and health". The contents about "Country-specific analysis on cultural factors in public health", "rapid transcultural adaptation" and "more specific practical experiences in diverse cultural backgrounds" were suggested to be added in future training. The participants considered that transcultural capacity ensured the smooth progress of GPHAC and they both could complement each other, transcultural adaptation was the premise of gaining trust and reaching cooperation, it can be conducive to the health assistance professionals to integrate into local cultural life, facilitating their foreign assistance work to be effective and efficient, and impart experiences well. The participants hoped to put the concept into action. CONCLUSION: The importance of transcultural competence in GPHAC is becoming a consensus of public health professionals. Enhanced transcultural competence reflected in the attitude of public health as well as other health workers would promote GPHAC and would foster efficient emergency health response management among many countries.

Research on the Mechanical Properties and Temperature Compensation of an Intelligent Pot Bearing for a Pipe-Type Welding Strain Gauge.

As an important component connecting the upper and lower structures of a bridge, bridge bearings can reliably transfer vertical and horizontal loads to a foundation. Bearing capacity needs to be monitored during construction and maintenance. To create an intelligent pot bearing, a portable small spot welding machine is used to weld pipe-type welding strain gauges to the pot bearing to measure strain and force values. The research contents of this paper include the finite element analysis of a basin bearing, optimal arrangement of welding strain gauges, calibration testing, and temperature compensation testing of the intelligent basin bearing of the welding strain gauges. Polynomial fitting is used for the fitting and analysis of test data. The results indicate that the developed intelligent pot bearing has a high-precision force measurement function and that after temperature compensation, the measurement error is within 1.8%. The intelligent pot bearing has a low production cost, and the pipe-type welding strain gauges can be conveniently replaced. The novelty is that the bearing adopts a robust pipe-type welding strain gauge and that automatic temperature compensation is used. Therefore, the research results have excellent engineering application value.

Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.

Vascular calcification (VC) is characterized by pathological depositions of calcium and phosphate in the arteries and veins via an active cell-regulated process, in which vascular smooth muscle cells (VSMCs) transform into osteoblast/chondrocyte-like cells as in bone formation. VC is associated with significant morbidity and mortality in chronic kidney disease (CKD) and cardiovascular disease, but the underlying mechanisms remain unclear. In this study we investigated the role of large-conductance calcium-activated potassium (BK) channels in 3 experimental VC models. VC was induced in vascular smooth muscle cells (VSMCs) by ß-glycerophosphate (ß-GP), or in rats by subtotal nephrectomy, or in mice by high-dosage vitamin D3. We showed that the expression of BK channels in the artery of CKD rats with VC and in ß-GP-treated VSMCs was significantly decreased, which was functionally confirmed by patch-clamp recording. In ß-GP-treated VSMCs, BK channel opener NS1619 (20 µM) significantly alleviated VC by decreasing calcium content and alkaline phosphatase activity. Furthermore, NS1619 decreased mRNA expression of ostoegenic genes OCN and OPN, as well as Runx2 (a key transcription factor involved in preosteoblast to osteoblast differentiation), and increased the expression of α-SMA protein, whereas BK channel inhibitor paxilline (10 µM) caused the opposite effects. In primary cultured VSMCs from BK-/- mice, BK deficiency aggravated calcification as did BK channel inhibitor in normal VSMCs. Moreover, calcification was more severe in thoracic aorta rings of BK-/- mice than in those of wild-type littermates. Administration of BK channel activator BMS191011 (10 mg· kg-1 ·d-1) in high-dosage vitamin D3-treated mice significantly ameliorated calcification. Finally, co-treatment with Akt inhibitor MK2206 (1 µM) or FoxO1 inhibitor AS1842856 (3 µM) in calcified VSMCs abrogated the effects of BK channel opener NS1619. Taken together, activation of BK channels ameliorates VC via Akt/FoxO1 signaling pathways. Strategies to activate BK channels and/or enhance BK channel expression may offer therapeutic avenues to control VC.

Associations of toothbrushing behaviour with risks of vascular and nonvascular diseases in Chinese adults.

Accumulating evidence has shown that poor oral hygiene is associated with increased risk of cardiometabolic diseases in Western populations. However, its relevance about the relationships in Chinese adults remains unclear. The China Kadoorie Biobank enrolled 512 715 adults aged 30-79 years in China during 2004-2008. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with measures of oral hygiene. Overall 9.3% of the participants reported rarely or never brushing teeth at baseline. Participants who rarely or never brushed teeth had adjusted HR of 1.12 (95% CI: 1.09, 1.15) for MVE, with similar HRs for stroke (1.08, 1.05-1.12), intracerebral haemorrhage (1.18, 1.11-1.26) and pulmonary heart disease (1.22, 1.13-1.32) compared with those who brushed teeth regularly. Those who did not brush teeth also had increased risk of cancer (1.09, 1.04-1.14), chronic obstructive pulmonary disease (COPD) (1.12, 1.05-1.20), liver cirrhosis (1.25, 1.09-1.44) and all-cause death (1.25, 1.21-1.28) but not type 2 diabetes (0.94, 0.86-1.03) and chronic kidney disease (0.98, 0.81-1.18). Among Chinese adults, we found that poor oral hygiene is associated with higher risks of major vascular disease, cancer, COPD, liver cirrhosis and all-cause deaths, but not type 2 diabetes and chronic kidney disease.

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.

Cigarette Smoking and Secondhand Smoke Exposure Before and After a Tobacco-Free Olympic Policy Period: Qingdao, China.

INTRODUCTION: We explored the impact of a temporary tobacco-free public policy for the 2008 Summer Olympics on the smoking prevalence and secondhand smoke exposure among the population of a co-hosting city, Qingdao, China. METHODS: The Qingdao Diabetes Survey was analyzed for 2006 (n = 4599) and 2009 (n = 4680), which are survey years before and after the tobacco-free Olympics public policy period (July 2007 to January 2009). We analyzed the differences in self-reported smoking prevalence and exposure to secondhand smoke at home and/or workplace, and compared odds of smoking by survey year and of exposure to secondhand smoke among nonsmokers. RESULTS: From 2006 to 2009, the male smoking prevalence declined from 51.4% (95% confidence interval [CI] = 49.0% to 53.9%) to 42.6% (95% CI = 40.2% to 45.1%), and the proportion of lighter smokers decreased more. Among nonsmokers, the secondhand smoke exposure rate declined from 62.2% (95% CI = 60.5% to 63.9%) to 56.8% (95% CI = 55.1% to 58.6%). Regression analyses show 34% lower odds of men smoking after Olympics (OR = 0.66, 95% CI = 0.57% to 0.77%). Rural residents and individuals who are not retired were more likely to smoke. Female nonsmokers report 17% less exposure to secondhand smoke after Olympics (OR = 0.83, 95% CI = 0.70% to 0.98%). Urban nonsmokers were more likely to be exposed than their rural counterparts. CONCLUSIONS: Smoking prevalence among men and secondhand smoke exposure among women significantly decreased in Qingdao, China, after the tobacco-free Olympics public policy period. As only the proportion of lighter smokers decreased, this may help explain why urban nonsmokers reported increased exposure. Unintended increased secondhand smoke exposure and cessation support need to be addressed in large-scale policy campaigns. IMPLICATIONS: Hosting the Olympic Games can help to initiate large-scale tobacco-free public policies for hosting cities. Although previous studies have demonstrated reduction in nonsmoker exposure to secondhand smoke, the impact on the hosting city's smoking prevalence or exposure rates is unclear. After the Olympic Games in Qingdao, China, smoking prevalence among men significantly decreased, mostly due to light smokers. Secondhand smoke exposure at home and/or workplace significantly decreased among female nonsmokers. Urban nonsmokers had an unintended consequence of increased secondhand smoke exposure after the tobacco-free Olympic policy period. Concurrent promotion of cessation support for heavier smokers may be needed.

Preparing Platelet-Rich Plasma with Whole Blood Harvested Intraoperatively During Spinal Fusion.

BACKGROUND Platelet-rich plasma (PRP) has gained growing popularity in use in spinal fusion procedures in the last decade. Substantial intraoperative blood loss is frequently accompanied with spinal fusion, and it is unknown whether blood harvested intraoperatively qualifies for PRP preparation. MATERIAL AND METHODS Whole blood was harvested intraoperatively and venous blood was collected by venipuncture. Then, we investigated the platelet concentrations in whole blood and PRP, the concentration of growth factors in PRP, and the effects of PRP on the proliferation and viability of human bone marrow-derived mesenchymal stem cells (HBMSCs). RESULTS Our results revealed that intraoperatively harvested whole blood and whole blood collected by venipuncture were similar in platelet concentration. In addition, PRP formulations prepared from both kinds of whole blood were similar in concentration of platelet and growth factors. Additional analysis showed that the similar concentrations of growth factors resulted from the similar platelet concentrations of whole blood and PRP between the two groups. Moreover, these two kinds of PRP formulations had similar effects on promoting cell proliferation and enhancing cell viability. CONCLUSIONS Therefore, intraoperatively harvested whole blood may be a potential option for preparing PRP spinal fusion.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Crosstalk between mesenchymal stem cells and macrophages in inflammatory bowel disease and associated colorectal cancer.

Mesenchymal stem cells (MSCs) are attractive seed cells for immunotherapy, tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities, diverse immunoregulatory functions and ease of isolation from a wide range of tissues. MSCs exert their immunoregulatory effect on immune cells via cell-to-cell contact and paracrine mechanisms. In turn, MSCs can also be modulated by immune cells. Macrophages are constantly present in the mucosa of the intestinal tract of mammals and play an important role in the development and progression of inflammatory bowel disease (IBD), a chronic and recurrent inflammatory disease of the gastrointestinal tract characterized by idiopathic mucosal inflammation. The increased morbidity and mortality of IBD have made it a disease hard to cure in the clinic. MSCs have emerged as an important tool for IBD therapy due to their abilities to differentiate into enterocyte-like cells and regulate inflammatory cells, especially macrophages. In this review, we discuss the recent advances in the interaction between MSCs and macrophages in diseases, with an emphasis on IBD. We propose that an optimized MSC-based therapy would provide a novel strategy for the treatment of IBD and the prevention of IBD-associated colorectal cancer (CRC).

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

Impact of a diabetes screening program on a rural Chinese population: a 3-year follow-up study.

BACKGROUND: Screening for type 2 diabetes helps detect previously unknown diabetes and identify people with pre-diabetes, but the adverse impact of such screening on individuals labelled as pre-diabetes or classified as normal, is less known. In this study the health-related quality of life (HRQoL), depression and lifestyle changes in a rural Chinese population are assessed three years after a screening program. METHODS: A total of 647 (39.1%) individuals with pre-diabetes and 1009 (60.9%) individuals with normoglycaemia from a population-based diabetes screening program in 2009 were re-examined in 2012-2013. Changes at the end of 3 years in HRQoL, depression, BMI, weight, frequency of physical activity and vegetable intake were assessed. RESULTS: In men with normoglycaemia the mean (SD) 15D scores were 0.974 (0.04) at baseline and 0.973 (0.05) at follow-up; and 0.971 (0.05) and 0.966 (0.06) for men with pre-diabetes. In women the scores were 0.973 (0.05) and 0.963 (0.06) for normoglycaemia and 0.959 (0.06) and 0.954 (0.07) for pre-diabetes, respectively. Compared to baseline, the HRQoL was slightly lower at 3 years in all groups but the change was not considered to be clinically important, and was only statistically significant for women with normoglycaemia (p < 0.05). The depression score was slightly elevated in women, but not in men. No significant changes in BMI were noticed, but weight increased slightly in the normoglycemia group (p < 0.05). Screening had a significant positive impact on physical activity and vegetable intake. CONCLUSIONS: This population-based diabetes screening program generated long-term positive changes toward a healthy lifestyle as measured by physical activity and vegetable intake for all the participants without adverse effects on the HRQoL and depression.

Association Between Serum Uric Acid and Prevalence of Type 2 Diabetes Diagnosed using HbA1c Criteria Among Chinese Adults in Qingdao, China.

OBJECTIVE: To determine whether elevated serum uric acid (UA) levels are associated with type 2 diabetes diagnosed using HbA1c levels among Chinese adults. METHODS: We conducted two population-based cross-sectional studies in Qingdao in China in 2006 and 2009. A total of 6894 (39.4% men) subjects aged 35-74 years were included in the data analysis. Newly diagnosed diabetes was defined as HbA1c level of ⋝6.5%, and prediabetes was classified as HbA1c level between 5.7% and 6.4% according to the International Diabetes Federation criteria. Multivariate logistic regression was employed to assess the association between UA and prevalence of type 2 diabetes defined using Glycated hemoglobin A1c (HbA1c) levels. RESULTS: Subjects with prediabetes had higher UA levels than those with normal glucose tolerance, newly diagnosed diabetes, and known diabetes, with corresponding values of 325.1 (82.5) µmol/L, 310.9 (84.2) µmol/L, 291.3 (81.7) µmol/L, 305.2 (83.6) µmol/L, respectively (P<0.001 for all comparisons). Binary logistic regression analysis showed that UA was a possible predictor for the prevalence of type 2 diabetes diagnosed using HbA1c levels, and the second quartile of UA levels had a higher odds ratio (OR: 4.088; 95% CI: 2.900-5.765) for HbA1c than the other quartiles after adjusting for age, body mass index, sex, marital status, education, income, alcohol consumption, smoking, and cardiometabolic parameters. CONCLUSION: Serum UA is significantly associated with type 2 diabetes diagnosed using HbA1c levels, independent of other cardiometabolic parameters.

Genetic and environmental effects on the bone development of the hand and wrist in Chinese young twins.

We assessed genetic and environmental effects on bone development of the hand and wrist, and on key anthropometric measures in Chinese young twins. In total, 139 monozygotic and 95 dizygotic twin pairs aged from 5 to 18 years were recruited. The twin correlations of total hand and wrist scores for monozygotic (MZ) and dizygotic (DZ) twins were 0.71 and 0.36, respectively. Bivariate model analysis showed moderate genetic correlations only for total skeletal maturity vs. weight and total skeletal maturity vs. waist circumference (r, 0.51 and 0.46, respectively). Our findings demonstrated that genetic factors played important roles in bone development of the hand and wrist in Chinese young twins, and that these genetic effects might be distinct from those influencing anthropometric measures.

Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans.

BACKGROUND: Oocyte secreted factors (OSFs), including growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play an important role in the process of follicular development and oocyte maturation. Since OSFs are expressed in oocytes and cumulus granulosa cells, the aim of the present study was to explore whether the expression levels of GDF9 and BMP15 mRNAs in cumulus granulosa cells can be used as molecular markers for predicting oocyte developmental potential. METHODS: Cumulus cells of 2426 cumulus-oocyte complexes were collected from 196 female patients who underwent intracytoplasmic sperm injection (ICSI) and were used for mRNA detection on the egg retrieval day. Pearson correlation analysis was used to analyze the correlation between OSF expression and general physiological parameters. Partial correlation analysis was used to analyze the correlation between OSF expression and oocyte developmental potential. Covariance analysis was used to compare OSF expression among different groups. Receiver operating characteristic curves were used to examine the diagnostic value of GDF9 and BMP15 mRNA for predicting pregnancy. RESULTS: The expression levels of GDF9 and BMP15 mRNAs were significantly associated with age, body mass index (BMI), oocyte maturation, normal fertilization, and cleavage rate (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the group with high-quality embryos were significantly higher than those in the group without high-quality embryos (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the pregnancy group were significantly higher than those in the nonpregnancy group (P < 0.05). The cut-off value of GDF9 mRNA for predicting pregnancy was 4.82, with a sensitivity of 82% and a specificity of 64%. The cut-off value of BMP15 mRNA for predicting pregnancy was 2.60, with a sensitivity of 78% and a specificity of 52%. CONCLUSIONS: The expression levels of GDF9 and BMP15 mRNAs were closely associated with oocyte maturation, fertilization, embryo quality, and pregnancy outcome; therefore, GDF9 and BMP15 mRNAs in cumulus granulosa cells may be considered as new molecular markers for predicting oocyte developmental potential.