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

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

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

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

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

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

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

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

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

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

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

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

Analysis of genetic and environmental correlation between leisure activities and cognitive function in aging Chinese twins.

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 (rG=0.80-0.96). Besides, intellectual activity and cognition presented low but significant unique environmental correlation (rE=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.

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

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

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

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

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

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

Pregnancy, pregnancy loss, and the risk of cardiovascular disease in Chinese women: findings from the China Kadoorie Biobank.

BACKGROUND: Pregnancy and pregnancy loss may be linked to cardiovascular disease (CVD). However, the evidence is still inconsistent, especially in East Asians, whose reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy, miscarriage, induced abortion, and stillbirth with CVD incidence among Chinese women. METHODS: In 2004-2008, the nationwide China Kadoorie Biobank recruited 302,669 women aged 30-79 years from ten diverse localities. During 7 years of follow-up, 43,968 incident cases of circulatory disease, 14,440 of coronary heart disease, and 19,925 of stroke (including 11,430 ischaemic and 2170 haemorrhagic strokes), were recorded among 289,573 women without prior CVD at baseline. Cox regression yielded multiple adjusted hazard ratios (HRs) for CVD risks associated with pregnancy outcomes. RESULTS: Overall, 99% of women had been pregnant, and among them 10%, 53%, and 7% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Each additional pregnancy was associated with an adjusted HR of 1.03 (95% confidence interval, CI: 1.02; 1.04) for circulatory disease. A history of miscarriage, induced abortion, and stillbirth, respectively, were associated with adjusted HRs of 1.04 (1.01; 1.07), 1.04 (1.02; 1.07), and 1.07 (1.03; 1.11) for circulatory disease. The relationship was stronger with recurrent pregnancy loss; adjusted HRs for each additional loss being 1.04 (1.00; 1.09) for miscarriage, 1.02 (1.01; 1.04) for induced abortion, and 1.04 (1.00; 1.08) for stillbirth. CONCLUSIONS: Among Chinese women, increases in pregnancy, and a history and recurrence of miscarriage, induced abortion, and stillbirth are each associated with a higher risk of CVD.

A genome-wide association study of cognitive function in Chinese adult twins.

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.

Genetic and Environmental Basis in Phenotype Correlation Between Physical Function and Cognition in Aging Chinese Twins.

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.

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

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

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

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

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

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

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

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

Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins.

Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins. Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents. Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population. Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.

The Qingdao Twin Registry: a status update.

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.

The association of pulse pressure change with memory decline in middle-aged and older adults.

BACKGROUND: Less is known regarding the association of pulse pressure (PP) with memory function. This study aimed to characterize long-term patterns of PP in middle-aged and older adults and explore their impact on subsequent change in memory function. METHODS: Data from the English Longitudinal Study of Ageing (ELSA, 2004-2018), were analyzed. Totally, 3587 dementia-free participants with three measurements of BP were included. All three visits of PP (2004-2012) were used to characterize longitudinal patterns of PP by group-based trajectory modeling (GBTM). Generalized estimating equation (GEE) models were fitted to explore the impact of PP trajectories on change in memory over a subsequent 6-year period (2012-2018). RESULTS: Using GBTM, three distinct trajectories of PP were identified: low-stable (38.1%), moderate-stable (48.6%), and elevated-increasing group (13.3%). GEE model suggested that memory declined over a 6-year period in all PP trajectories (all Ptime <0.001). The overall interactions between patterns of PP changes and time with memory were statistically significant (χ2 interaction  = 20.69, p = 0.002). Compared to participants in the low-stable group, those in the moderate-stable and elevated-increasing group exhibited a faster decline in memory. CONCLUSIONS: Longitudinal patterns of moderate-stable and elevated-increasing PP were associated with an accelerated decrease in memory. Controlling BP instability may be a promising interventional strategy for preventing cognitive decline among older adults.