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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]

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

Although the correlation between cognition and physical function has been well studied in the general population, the genetic and environmental nature of the correlation has been rarely investigated. We conducted a classical twin analysis on cognitive and physical function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), handgrip strength, five-times-sit-to-stand test (FTSST), near visual acuity, and number of teeth lost in 379 complete twin pairs. Bivariate twin models were fitted to estimate the genetic and environmental correlation between physical and cognitive function. Bivariate analysis showed mildly positively genetic correlations between cognition and FEV1, r G = 0.23 [95% CI: 0.03, 0.62], as well as FVC, r G = 0.35 [95% CI: 0.06, 1.00]. We found that FTSST and cognition presented very high common environmental correlation, r C = -1.00 [95% CI: -1.00, -0.57], and low but significant unique environmental correlation, r E = -0.11 [95% CI: -0.22, -0.01], all in the negative direction. Meanwhile, near visual acuity and cognition also showed unique environmental correlation, r E = 0.16 [95% CI: 0.03, 0.27]. We found no significantly genetic correlation for cognition with handgrip strength, FTSST, near visual acuity, and number of teeth lost. Cognitive function was genetically related to pulmonary function. The FTSST and cognition shared almost the same common environmental factors but only part of the unique environmental factors, both with negative correlation. In contrast, near visual acuity and cognition may positively share part of the unique environmental factors. [ABSTRACT FROM AUTHOR]

Systolic and diastolic blood pressure, pulse pressure (PP), and body mass index (BMI) are heritable traits in human metabolic health but their common genetic and environmental backgrounds are not well investigated. The aim of this article was to explore the phenotypic and genetic associations among PP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. The studied sample contained 615 twin pairs (17–84 years) collected in the Qingdao municipality. Univariate and multivariate structural equation models were fitted for assessing the genetic and environmental contributions. The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for each four phenotypes. Heritability estimated in univariate analysis ranged from 0.42 to 0.74 with the highest for BMI (95% CI 0.70–0.78), and the lowest for PP (95% CI 0.34–0.49). The multivariate model estimated (1) high genetic correlations for DBP with SBP (0.87), PP with SBP (0.75); (2) low–moderate genetic correlations between PP and DBP (0.32), each BP component and BMI (0.24–0.37); (3) moderate unique environmental correlation for PP with SBP (0.68) and SBP with DBP (0.63); (4) there was no significant unique environmental correlation between PP and BMI. Overall, our multivariate analyses revealed common genetic and environmental backgrounds for PP, BP, and BMI in Chinese twins. [ABSTRACT FROM PUBLISHER]

Aim Previous studies have shown that uric acid ( UA) has strong anti-oxidant properties, and that high circulating levels of UA are prospectively associated with improved muscle function and cognitive performances in elderly Caucasians. We carried out a replication study in elderly Chinese using cross-sectional design. Methods Data from 2006 individuals aged 50-74 years who participated in a population-based cross-sectional survey in Qingdao, China, were analyzed. Hand grip strength was measured in kilograms by using an electronic dynamometer. The sit-to-stand ( STS) test time was used to represent lower limb strength. The Mini- Mental State Examination ( MMSE) was used to estimate the participants' cognitive function. Lifestyle, comorbidities and laboratory measures were considered as potential confounders. Multiple linear regression models and binary logistic regression were fitted to find the association of UA with strength measures and cognitive performances. Results Participants were grouped according to UA tertiles (<257.75 mmol/ L, ≥257.75 and ≤359.00 mmol/ L, >359.00 mmol/ L). Hand grip strength significantly increased across UA tertiles (26.4 ± 8.5 kg; 30.1 ± 10.5 kg; 35.0 ± 11.4 kg; P < 0.001), and prevalence of cognitive disorder declined across UA tertiles (7.9%, 4.9%, 3.1%; P = 0.012). After adjusting for potential confounders, high UA level remained significantly associated with high grip strength ( P = 0.023) and decreased risk of cognitive disorder with an OR of 1.002 (95% CI 1.000-1.004; P = 0.022). However, UA level was not significantly associated with STS time ( P = 0.780). Conclusions Our findings suggested that notwithstanding the associated increased risk of cardiovascular disease, UA might play a protective role in aging-associated decline in muscle strength and cognitive function. Geriatr Gerontol Int 2013; 13: 672-677. [ABSTRACT FROM AUTHOR]

In 1998, the Qingdao Twin Registry was initiated as the main part of the Chinese National Twin Registry. By 2005, a total of 10,655 twin pairs had been recruited. Since then new twin cohorts have been sampled, with one longitudinal cohort of adolescent twins selected to explore determinants of metabolic disorders and health behaviors during puberty and young adulthood. Adult twins have been sampled for studying heritability of multiple phenotypes associated with metabolic disorders. In addition, an elderly twin cohort has been recruited with a focus on genetic studies of aging-related phenotypes using twin modeling and genome-wide association analysis. Cross-cultural collaborative studies have been carried out between China, Denmark, Finland, and US cohorts. Ongoing data collection and analysis for the Qingdao Twin Registry will be discussed in this article. [ABSTRACT FROM AUTHOR]

Aim: Studies carried out in Western populations have shown age-related changes in multiple health domains together with gender-specific patterns. By focusing on five health domains, self-rated health, hand grip strength, sit-to-stand test, cognitive performance and depression, we examined the age trajectories in general health in a cross-sectional Chinese sample representing the world's largest ethnic population and compare with Danish data that represent Western populations in developed countries. Methods: Multiple regression models were fitted to compare patterns across genders and populations together with gender- and population-specific patterns in age-related decline. Results: Better self-rated health for males than for females was observed in both countries, and Danes reported better health than the Chinese for both genders. For hand grip strength, significant gender differences were shown across countries and significant population differences observed in Danish and Chinese males. There was no population difference in sit-to-stand time across genders. Female Danes outperformed males in cognitive performance. No significant gender differences in depression were observed in both populations. Conclusion: Our cross population analysis identified significant gender and population differences suggesting endogenous biological, physical and social environmental determinants in age-related decline in general health. Geriatr Gerontol Int 2012; 12: 431-439. [ABSTRACT FROM AUTHOR]

The genetic loci affecting the commonly used BMI have been intensively investigated using linkage approaches in multiple populations. This study aims at performing the first genome-wide linkage scan on BMI in the Chinese population in mainland China with hypothesis that heterogeneity in genetic linkage could exist in different ethnic populations. BMI was measured from 126 dizygotic twins in Qingdao municipality who were genotyped using high-resolution Affymetrix Genome-Wide Human SNP arrays containing about 1 million single-nucleotide polymorphisms (SNPs). Nonparametric linkage analysis was performed with Merlin software package for linkage analysis using variance components approach for quantitative trait loci mapping. We identified a strong linkage peak at the end of chromosome 7 (7q36 at 186 cM) with a lod score of 4.06 which overlaps with that reported by a large multicenter study in western countries. Multiple loci showing suggestive linkage were found on chromosome 1 (lod score 2.38 at 242 cM), chromosome 8 (2.48 at 95 cM), and chromosome 14 (2.2 at 89.4 cM). The strong linkage identified in the Chinese subjects that is consistent with that found in populations of European origin could suggest the existence of evolutionarily preserved genetic mechanisms for BMI whereas the multiple suggestive loci could represent genetic effect from gene-environment interaction as a result of population-specific environmental adaptation. [ABSTRACT FROM AUTHOR]

• WWC1 rs17070145 was marginally associated with AD and VaD in older adults. • WWC1 exonic SNPs rs3822660 and rs3822659 are in strong LD with rs17070145. • The strong LD may explain the association of WWC1 rs17070145 C allele with AD. • Stroke may partly explain the association of rs17070145 CC genotype with VaD. We sought to examine the associations of common WWC1 variants with Alzheimer's disease (AD) and vascular dementia (VaD) among rural-dwelling older adults in China. This population-based study used data from the baseline assessments (March –September 2018) of MIND-China. AD and VaD were diagnosed following the international criteria. Of the 5455 participants (age≥60 years, 57.27% women), 182 were diagnosed with AD and 88 with VaD. Logistic regression analysis suggested that WWC1 rs17070145 C allele (vs. T) was associated with multivariable-adjusted odds ratio of 1.23 (95% confidence interval 0.96–1.58) for AD, and that CC genotype (vs. TT) was associated with multivariable-adjusted odds ratio of 2.19(1.10–4.39) for VaD, but the association with VaD became non-significant when further adjusting for stroke history. Furthermore, exonic SNPs rs3822660 and rs3822659 were in strong linkage disequilibrium (LD) with rs17070145 (D' = 0.88). These results suggest that the strong LD between rs17070145 and 2 exonic SNPs may explain the association of WWC1 rs17070145 C allele with AD and that stroke may partly explain the association of WWC1 rs17070145 CC genotype with VaD. [ABSTRACT FROM AUTHOR]

On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs. [ABSTRACT FROM AUTHOR]

Obesity is an established risk factor for hyperuricemia, but the mechanisms are only partially understood. We examined whether BMI-related DNA methylation (DNAm) variation would mediate the association of BMI with serum uric acid (SUA). We first conducted an epigenome-wide association analysis (EWAS) in 64 monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediated effect of DNAm using mediation analysis. Ontology enrichments analysis was performed for CpGs using GREAT tool. The genes where the candidate CpG mediators mapped were validated using gene expression data. BMI was positively associated with log 10 transformed SUA level (β = 0.01, P < 0.001). The association between BMI and DNAm of 138 CpGs reached P < 1 × 10 -4 level. Twenty BMI-related differentially methylated regions within MAP2K2, POU4F2, AGAP2, MRGPRE, ADM5, and NKX1-1 were found. Of the 138 CpGs, 4 within VENTX (involved in cellular responses to stress pathway), SMOC2 (enable calcium ion binding), and FSCN2 (a member of fascin protein family) mediated the association between BMI and SUA, with a mediating effect of 0.002-μmol/L lower log 10 transformed SUA levels and a proportion of 18.89 %-24.92 % negative mediating effect. BMI × DNAm interactions on SUA were observed for 2 CpGs within VENTX. The gene expression level of VENTX was also negatively associated with SUA level. BMI-related DNAm variation may partially mediate the association of BMI with SUA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Leisure activity has been shown to be beneficial to mental health and cognitive aging. The biological basis of the correlation is, however, poorly understood. This study aimed at exploring the genetic and environmental impacts on correlation between leisure activities and cognitive function in the Chinese middle- and old-aged twins., Methods: Cognition measured using a screening test (Montreal Cognitive Assessment, MoCA) and leisure activities including intellectual and social activity were investigated on 379 complete twin pairs of middle- and old-aged twins. Univariate and bivariate twin models were fitted to estimate the genetic and environmental components in their variance and covariance., Results: Moderate heritability was estimated for leisure activities and cognition (0.44-0.53) but insignificant for social activity. Common environmental factors accounted for about 0.36 of the total variance to social activity with no significant contribution to leisure activity, intellectual activity and cognition. Unique environmental factors displayed moderate contributions (0.47-0.64) to leisure activities and cognition. Bivariate analysis showed highly and positively genetic correlations between leisure activities and cognition (r G =0.80-0.96). Besides, intellectual activity and cognition presented low but significant unique environmental correlation (r E =0.12)., Conclusions: Genetic factor had the moderate contribution to leisure activities and cognition. Cognitive function was highly genetically related to leisure activities. Intellectual activity and cognitive function may share some unique environmental basis.

Background: Extensive epidemiological studies have established the association between exposure to early-life adversity and health status and diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans is sparse. The Great Chinese Famine lasting from 1958 to 1961 is a natural string of disasters offering a precious opportunity for elucidating the underlying epigenetic mechanism of the long-term effect of early adversity., Methods: Using a high-throughput array platform for DNA methylome profiling, we conducted a case-control epigenome-wide association study on early-life exposure to Chinese famine in 79 adults born during 1959-1961 and compared to 105 unexposed subjects born 1963-1964., Results: The single CpG site analysis of whole epigenome revealed a predominant pattern of decreased DNA methylation levels associated with fetal exposure to famine. Four CpG sites were detected with p < 1e-06 (linked to EHMT1, CNR1, UBXN7 and ESM1 genes), 16 CpGs detected with 1e-06 < p < 1e-05 and 157 CpGs with 1e-05 < p < 1e-04, with a predominant pattern of hypomethylation. Functional annotation to genes and their enriched biological pathways mainly involved neurodevelopment, neuropsychological disorders and metabolism. Multiple sites analysis detected two top-rank differentially methylated regions harboring RNF39 on chromosome 6 and PTPRN2 on chromosome 7, both showing epigenetic association with stress-related conditions., Conclusion: Early-life exposure to famine could mediate DNA methylation regulations that persist into adulthood with broad impacts in the activities of genes and biological pathways. Results from this study provide new clues to the epigenetic embedding of early-life adversity and its impacts on adult health., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cognitive ability plays an important role in mental and physical well-beings in the increasingly ageing populations. Here, based on a sample of 30 cognitive function-discordant monozygotic twin pairs, we aimed to detect specific epigenetic variants potentially related to cognitive function by conducting an epigenome-wide association study (EWAS). Association between methylation level of single CpG site with cognitive function score was tested by linear mixed effect model. Functions of cis-regulatory regions and ontology enrichments were predicted by Genomic Regions Enrichment of Annotations Tool (GREAT). Differentially methylated regions (DMRs) were detected by comb-p python library. A list of 28 CpG sites were identified to reach the level of P < 1 × 10 -4 , and the strongest association (cor = 0.138, P = 2.549 × 10 -6 ) was detected for DNA CpG site (Chr17: 40,700,490 bp) located at HSD17B1P1. The identified 14,065 genomic CpG sites (P < 0.05) were mapped to 2646 genes, especially HSD17B1P1, CUL4A, INTS8, GFI1B, ZNF467, CDH15, and PSMA1. GREAT ontology enrichments mainly highlighted nicotine pharmacodynamics pathway, GABA-B receptor II/nicotinic acetylcholine receptor/hedgehog/endothelin/Wnt signaling pathways, Parkinson disease, Huntington disease, glycolysis, neuronal system, and toll-like receptor binding. We detected 15 DMRs located at/near 16 genes, especially LINC01551, LINC02282, and FAM32A. And 32 cognitive function-associated differentially methylated genes could be replicated, such as SHANK2, ABCA2, PRDM16, NCOR2, and INPP5A. Our EWAS in monozygotic twins identify specific epigenetic variations which are significantly involved in functional genes, biological function and pathways that mediate cognitive function. The findings provide clues to further identify new diagnostic biomarkers and therapeutic targets for cognitive dysfunction., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care., Objective: To explore sex differences in genetic associations with longevity., Design Setting and Participants: This population-based case-control study used sex-specific genome-wide association study and polygenic risk score (PRS) analyses to examine sex differences in genetic associations with longevity. Five hundred sixty-four male and 1614 female participants older than 100 years were compared with a control group of 773 male and 1526 female individuals aged 40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study participants with Han ethnicity who were recruited in 1998 and 2008 to 2014., Main Outcomes and Measures: Sex-specific loci and pathways associated with longevity and PRS measures of joint effects of sex-specific loci., Results: Eleven male-specific and 11 female-specific longevity loci ( P < 10 -5 ) and 35 male-specific and 25 female-specific longevity loci (10 -5 ≤ P < 10 -4 ) were identified. Each of these loci's associations with longevity were replicated in north and south regions of China in one sex but were not significant in the other sex ( P = .13-.97), and loci-sex interaction effects were significant ( P < .05). The associations of loci rs60210535 of the LINC00871 gene with longevity were replicated in Chinese women ( P = 9.0 × 10 -5 ) and US women ( P = 4.6 × 10 -5 ) but not significant in Chinese and US men. The associations of the loci rs2622624 of the ABCG2 gene were replicated in Chinese women ( P = 6.8 × 10 -5 ) and European women ( P = .003) but not significant in both Chinese and European men. Eleven male-specific pathways (inflammation and immunity genes) and 34 female-specific pathways (tryptophan metabolism and PGC-1α induced) were significantly associated with longevity ( P < .005; false discovery rate < 0.05). The PRS analyses demonstrated that sex-specific associations with longevity of the 4 exclusive groups of 11 male-specific and 11 female-specific loci ( P < 10 -5 ) and 35 male-specific and 25 female-specific loci (10 -5 ≤ P < 10 -4 ) were jointly replicated across north and south discovery and target samples. Analyses using the combined data set of north and south showed that these 4 groups of sex-specific loci were jointly and significantly associated with longevity in one sex ( P = 2.9 × 10 -70 to 1.3 × 10 -39 ) but not jointly significant in the other sex ( P = .11 to .70), while interaction effects between PRS and sex were significant ( P = 4.8 × 10 -50 to 1.2 × 10 -16 )., Conclusion and Relevance: The sex differences in genetic associations with longevity are remarkable, but have been overlooked by previously published genome-wide association studies on longevity. This study contributes to filling this research gap and provides a scientific basis for further investigating effects of sex-specific genetic variants and their interactions with environment on healthy aging, which may substantially contribute to more effective and targeted individualized health care for male and female elderly individuals., Competing Interests: Conflict of Interest Disclosures: Dr Bai reported grants from the Natural Science Foundation of China during the conduct of the study. Dr Ni reported grants from the National Basic Research Program of China during the conduct of the study. Dr Slagboom reported grants from government during the conduct of the study. Dr Gottschalk reported serving as a consultant for Zinfandel Pharmaceuticals Inc outside the submitted work and was supported by National Institute on Aging grant RO1 AG040370. No other disclosures were reported.

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

Objective: The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments., Materials and Methods: The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18-65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23-64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype., Results: Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits., Conclusion: Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples.

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.)

Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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

Although the phenotypic correlation between systolic blood pressure (SBP) and diastolic blood pressure (DBP) is well known, the genetic basis for the correlation has rarely been investigated. The aim of this paper is to examine the genetic overlap between SBP and DBP by fitting bivariate models to Danish and Chinese twins and comparing ethnic differences between the two samples. Our estimates revealed a high proportion of additive genetic components shared by both SBP and DBP in Danish (0.71, 95% confidence interval (CI): 0.65-0.75) and Chinese (0.62, 95% CI: 0.50-0.71) twins with no statistically significant ethnic differences. The estimated genetic component in phenotypic correlation could serve to guide molecular genetic studies searching for genetic variants that affect both SBP and DBP. The bivariate model also estimated genetic and environmental contributions to SBP and DBP separately, with an overall pattern of higher genetic regulation or heritability in Danish (0.72, 95% CI: 0.67-0.76 for SBP; 0.70, 95% CI: 0.65-0.75 for DBP) than in Chinese (0.54, 95% CI: 0.44-0.63 for SBP; 0.57, 95% CI: 0.47-0.65 for DBP) twins and a higher contribution from unique environmental factors in Chinese compared with Danish twins. The estimated contribution from unique environmental factors suggests that promoting healthy lifestyles may provide an efficient way of controlling high blood pressure, particularly in the Chinese population.

Background: Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap., Method: We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes and social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods., Results: Interaction between regular exercise and carrying rs1042718 minor allele is significantly and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers., Conclusions: The results indicate significant positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings are exploratory rather than causal conclusions. This study implies that near-future health promotion programs considering individuals' genetic profiles, with appropriate protection of privacy/confidentiality, would yield increased benefits and reduced costs to the programs and their participants.

Objectives: A twin-based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed., Design and Methods: Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18-67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18-69). Twin modeling was performed on full and nested models with the best fitting models selected., Results: Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins., Conclusions: Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions., (Copyright © 2012 The Obesity Society.)

Elevated pulse pressure (PP) is associated with cardiovascular disorders and mortality in various populations. The genetic influence on PP has been confirmed by heritability estimates using related individuals. Recently, efforts have been made by mapping genes that are linked to the phenotype. We report the results of our gene mapping studies conducted in the Chinese population in mainland China. The genome-wide linkage and association scans were carried out on 63 middle-aged dizygotic twin pairs using high-density markers. The linkage analysis identified three significant linkage peaks (all with a single point P<1e(-05)) on chromosome 11 (LOD core 4.06 at 30.5 cM), chromosome 12 (LOD score 3.97 at 100.7 cM) and chromosome 18 (LOD score 4.01 at 70.7 cM), with the last two peaks closely overlapping with linkage peaks reported by two American studies. Multiple regions with suggestive linkages were identified, with many of the peaks overlapping with published linkage regions. The genome-wide association analysis detected a suggestive association on chromosome 4 (rs17031508, P<8.34e(-08)) located within a wide region of suggestive linkage. Our results provide some evidence for genetic linkages and associations with PP in the Chinese population. Further investigation is warranted to replicate the findings and to explore the susceptibility loci or genes for PP.

By focusing on four health variables, handgrip strength, near visual acuity, tooth loss and hearing level, this study examined the different patterns of age-related changes in these variables in Chinese aged from 50 to 74 years, as well as explored the relationship among the variables in a cross-sectional sample of 2006 individuals. The data exhibited high quality with a low missing rate of under 5% in any age groups for each variable. Effects of age and sex on the changes in the four health variables were assessed using multiple regression models with age and sex interactions included. Upon the highly significant effects of age on all four measurements, we observed substantially higher grip strength for men who, however, exhibited a faster age-related decline than for women. No sex difference or age-sex interaction was found in the number of teeth lost. Near visual acuity displayed a faster age-related decline in women than in men but neither the overall sex difference nor age-sex interaction reached statistical significance. For hearing function, while no sex difference was found at middle frequency, women had better sensitivity at high frequency and men were more sensitive at low frequency. Multivariate analysis did not support an age-related common mechanism underlying the four health variables., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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.