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BACKGROUND: Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks. METHODS: By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs). FINDINGS: Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18-0.19) to 0.23 (95% CI 0.23-0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs â COVID-19 â CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks. INTERPRETATION: Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of 'Long COVID-19.'
Subject(s)
COVID-19 , Coronary Disease , Humans , Bayes Theorem , Post-Acute COVID-19 Syndrome , COVID-19/genetics , Coronary Disease/epidemiology , Coronary Disease/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Genetic Loci , Genome-Wide Association StudyABSTRACT
Limited research has reported the association between MTNR1B gene polymorphisms and ischemic stroke (IS), and there is insufficient evidence on whether adopting a healthy lifestyle can mitigate genetic risks in this context. This study aimed to investigate the associations between MTNR1B gene variants (rs10830963 and rs1387153) and IS, examining the potential effect of gene-lifestyle interactions on IS risk. Conducted in northern China, this family-based cohort study involved 5116 initially IS-free subjects. Genotype data for rs10830963 and rs1387153 in MTNR1B were collected. Eight modifiable lifestyle factors, including body mass index (BMI), smoking, alcohol consumption, dietary habits, physical activity, sedentary time, sleep duration, and chronotype, were considered in calculating healthy lifestyle scores. Multilevel Cox models were used to examine the associations between MTNR1B variants and IS. Participants carrying the rs10830963-G and rs1387153-T alleles exhibited an elevated IS risk. Each additional rs10830963-G allele and rs1387153-T allele increased the IS risk by 36% (HR = 1.36, 95% CI, 1.12-1.65) and 32% (HR = 1.32, 95% CI, 1.09-1.60), respectively. Participants were stratified into low, medium, and high healthy lifestyle score groups (1537, 2188, and 1391 participants, respectively). Genetic-lifestyle interactions were observed for rs10830963 and rs1387153 (p for interaction < 0.001). Notably, as the healthy lifestyle score increased, the effect of MTNR1B gene variants on IS risk diminished (p for trend < 0.001). This study underscores the association between the MTNR1B gene and IS, emphasizing that adherence to a healthy lifestyle can mitigate the genetic predisposition to IS.
Subject(s)
Healthy Lifestyle , Ischemic Stroke , Receptor, Melatonin, MT2 , Humans , Receptor, Melatonin, MT2/genetics , Male , Female , Middle Aged , China/epidemiology , Ischemic Stroke/genetics , Ischemic Stroke/epidemiology , Cohort Studies , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease , Adult , AgedABSTRACT
INTRODUCTION: 'Let's Talk About Children' is a brief family focused intervention developed to improve mental health outcomes of children of parents with mental illness (COPMI). This study aims to assess the efficacy of LTC in improving mental health of children of parents with schizophrenia or bipolar disorder in China. METHODS: The planned study is a multicentre parallel group randomized wait-list controlled trial. A total of 400 eligible families with children aged 8 to 18 years will be recruited, 200 each for families with parental schizophrenia or bipolar disorder. The intervention group will receive Let's Talk About Children delivered by a trained therapist, while the control group will receive treatment as usual. The primary outcomes are child mental health measured by the strengths and difficulties questionnaire and parent-child communication measured using the parent-adolescent communication scale. Parental mental health and family functioning are secondary outcomes. This study also plans to explore mediating factors for the effect of Let's Talk About Children on child mental health, as well as conduct a cost-effectiveness analysis on using Let's Talk About Children in China. CONCLUSION: The present study will provide evidence for the efficacy of Let's Talk About Children in families with parental schizophrenia and bipolar disorder in China. In addition, it will evaluate potential mechanisms of action and cost-effectiveness of Let's Talk About Children, providing a basis for future implementation. TRIAL REGISTRATION: ChiCTR2300073904.
Subject(s)
Bipolar Disorder , Neurodevelopmental Disorders , Schizophrenia , Adolescent , Humans , Bipolar Disorder/therapy , Schizophrenia/therapy , Parents/psychology , Mental Health , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
BACKGROUND: Muscle mass loss is an age-related process that can be exacerbated by lifestyle, environmental and other factors, but can be mitigated by good sleep. The objective of this study was to investigate the correlation between varying time lags of sleep duration and the decline in muscle mass among individuals aged 60 years or older by using real-world health monitoring data obtained from wearable devices and smart home health monitoring devices. METHODS: This study included 86,037 observations from 2,869 participants in the Mobile Support System database. Missing data were supplemented by multiple imputation. The investigation utilized generalized estimating equations and restricted cubic spline curve to examine the relationship between sleep duration and low muscle mass. Various lag structures, including 0, 1, 2, 0-1, 0-2, and 1-2 months, were fitted, and the interaction effect of observation time with sleep duration was estimated for each lag structure. Additionally, subgroup analyses were conducted. The models were adjusted for various covariates, including gender, age, body mass index, footsteps, smoking status, drinking status, marital status, number of chronic diseases, number of medications, diabetes mellitus, hyperlipidemia, coronary artery disease, respiratory disease, and musculoskeletal disease and an interaction term between time and sleep duration. RESULTS: The results of the generalized estimating equation showed a significant correlation (p < 0.001) between sleep duration of 8 h or more and low muscle mass in older adults, using 6-7 h of sleep as a reference. This effect was seen over time and prolonged sleep accumulated over multiple months had a greater effect on muscle mass loss than a single month. The effect of long sleep duration on muscle mass loss was significantly greater in females than in males and greater in the over-75 than in the under-75 age group. Restricted cubic spline plots showed a non-linear relationship between sleep duration and low muscle mass (p < 0.001). CONCLUSIONS: This study found an association between sustained nighttime sleep of more than eight hours and decreased muscle mass in older adults, especially older women.
Subject(s)
Independent Living , Sleep , Humans , Male , Female , Aged , Middle Aged , China/epidemiology , Sleep/physiology , Time Factors , Sarcopenia/epidemiology , Aged, 80 and over , Muscle, Skeletal/physiology , East Asian PeopleABSTRACT
INTRODUCTION: An increasing number of original studies suggested that occupational noise exposure might be associated with the risk of hypertension, but the results remain inconsistent and inconclusive. In addition, the attributable fraction (AF) of occupational noise exposure has not been well quantified. We aimed to conduct a large-scale occupational population-based study to comprehensively investigate the relationship between occupational noise exposure and blood pressure and different hypertension subtypes and to estimate the AF for hypertension burden attributable to occupational noise exposure. METHODS: A total of 715,135 workers aged 18-60 years were included in this study based on the Key Occupational Diseases Surveillance Project of Guangdong in 2020. Multiple linear regression was performed to explore the relationships of occupational noise exposure status, the combination of occupational noise exposure and binaural high frequency threshold on average (BHFTA) with systolic and diastolic blood pressure (SBP, DBP). Multivariable logistic regression was used to examine the relationshipassociation between occupational noise exposure status, occupational noise exposure combined with BHFTA and hypertension. Furthermore, the attributable risk (AR) was calculated to estimate the hypertension burden attributed to occupational exposure to noise. RESULTS: The prevalence of hypertension among occupational noise-exposed participants was 13·7%. SBP and DBP were both significantly associated with the occupational noise exposure status and classification of occupational noise exposure combined with BHFTA in the crude and adjusted models (all P < 0·0001). Compared with workers without occupational noise exposure, the risk of hypertension was 50% greater among those exposed to occupational noise in the adjusted model (95% CI 1·42-1·58). For participants of occupational noise exposed with BHFTA normal, and occupational noise exposed with BHFTA elevated, the corresponding risks of hypertension were 48% (1·41-1·56) and 56% (1·46-1·63) greater than those of occupational noise non-exposed with BHFTA normal, respectively. A similar association was found in isolated systolic hypertension (ISH) and prehypertension. Subgroup analysis by sex and age showed that the positive associations between occupational noise exposure and hypertension remained statistically significant across all subgroups (all P < 0.001). Significant interactions between occupational noise status, classification of occupational noise exposure combined with BHFTA, and age in relation to hypertension risk were identified (all P for interaction < 0.001). The associations of occupational noise status, classification of occupational noise exposure combined with BHFTA and hypertension were most pronounced in the 18-29 age groups. The AR% of occupational noise exposure for hypertension was 28·05% in the final adjusted model. CONCLUSIONS: Occupational noise exposure was positively associated with blood pressure levels and the prevalence of hypertension, ISH, and prehypertension in a large occupational population-based study. A significantly increased risk of hypertension was found even in individuals with normal BHFTA exposed to occupational noise, with a further elevated risk observed in those with elevated BHFTA. Our findings provide epidemiological evidence for key groups associated with occupational noise exposure and hypertension, and more than one-fourth of hypertension cases would have been prevented by avoiding occupational noise exposure.
Subject(s)
Hearing Loss, Noise-Induced , Hypertension , Noise, Occupational , Occupational Diseases , Occupational Exposure , Prehypertension , Humans , Noise, Occupational/adverse effects , Cross-Sectional Studies , Hypertension/epidemiology , Hypertension/etiology , Occupational Exposure/adverse effects , Occupational Exposure/analysis , Occupational Diseases/epidemiology , Hearing Loss, Noise-Induced/etiology , China/epidemiologyABSTRACT
BACKGROUND: The paucity of evidence on longitudinal and consecutive recordings of physical activity (PA) and blood pressure (BP) under real-life conditions and their relationships is a vital research gap that needs to be addressed. OBJECTIVE: This study aims to (1) investigate the short-term relationship between device-measured step volume and BP; (2) explore the joint effects of step volume and variability on BP; and (3) examine whether the association patterns between PA and BP varied across sex, hypertension status, and chronic condition status. METHODS: This study used PA data of a prospective cohort of 3070 community-dwelling older adults derived from a mobile health app. Daily step counts, as a proxy of step volume, were derived from wearable devices between 2018 and 2022 and categorized into tertiles (low, medium, and high). Step variability was assessed using the SD of daily step counts. Consecutive daily step count recordings within 0 to 6 days preceding each BP measurement were analyzed. Generalized estimation equation models were used to estimate the individual and joint associations of daily step volume and variability with BP. Stratified analyses by sex, the presence of hypertension, and the number of morbidities were further conducted. RESULTS: A total of 3070 participants, with a median age of 72 (IQR 67-77) years and 71.37% (2191/3070) women, were included. Participants walked a median of 7580 (IQR 4972-10,653) steps and 5523 (IQR 3590-7820) meters per day for a total of 592,597 person-days of PA monitoring. Our results showed that higher levels of daily step volume were associated with lower BP (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure). Compared with participants with low step volume (daily step counts <6000/d) and irregular steps, participants with high step volume (≥9500/d) and regular steps showed the strongest decrease in systolic BP (-1.69 mm Hg, 95% CI -2.2 to -1.18), while participants with medium step volume (6000/d to <9500/d) and regular steps were associated with the lowest diastolic BP (-1.067 mm Hg, 95% CI -1.379 to -0.755). Subgroup analyses indicated generally greater effects on women, individuals with normal BP, and those with only 1 chronic disease, but the effect pattern was varied and heterogeneous between participants with different characteristics. CONCLUSIONS: Increased step volume demonstrated a substantial protective effect on BP among older adults with chronic conditions. Furthermore, the beneficial association between step volume and BP was enhanced by regular steps, suggesting potential synergistic protective effects of both increased step volume and step regularity. Targeting both step volume and variability through PA interventions may yield greater benefits in BP control, particularly among participants with hypertension and a higher chronic disease burden.
Subject(s)
Blood Pressure , Hypertension , Wearable Electronic Devices , Humans , Aged , Female , Male , Longitudinal Studies , Hypertension/physiopathology , Prospective Studies , Exercise , China , Middle Aged , Aged, 80 and over , Mobile Applications , East Asian PeopleABSTRACT
OBJECTIVE: The objective of this study is to investigate the gene-gene interactions associated with NSCL/P among DNA repair genes. DESIGN: This study included 806 NSCL/P case-parent trios from China. Quality control process was conducted for genotyped single nucleotide polymorphisms (SNPs) located in six DNA repair genes (ATR, ERCC4, RFC1, TYMS, XRCC1 and XRCC3). We tested gene-gene interactions with Cordell's method using statistical package TRIO in R software. Bonferroni corrected significance level was set as P = 4.24 × 10-4. We also test the robustness of the interactions by permutation tests. SETTING: Not applicable. PATIENTS/PARTICIPANTS: A total of 806 NSCL/P case-parent trios (complete trios: 682, incomplete trios: 124) with Chinese ancestry. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Not applicable. RESULTS: A total of 118 SNPs were extracted for the interaction tests. Fourteen pairs of significant interactions were identified after Bonferroni correction, which were confirmed in permutation tests. Twelve pairs were between ATR and ERCC4 or XRCC3. The most significant interaction occurred between rs2244500 in TYMS and rs3213403 in XRCC1(P = 8.16 × 10-15). CONCLUSIONS: The current study identified gene-gene interactions among DNA repair genes in 806 Chinese NSCL/P trios, providing additional evidence for the complicated genetic structure underlying NSCL/P. ATR, ERCC4, XRCC3, TYMS and RFC1 were suggested to be possible candidate genes for NSCL/P.
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OBJECTIVE: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies. METHODS: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results. RESULTS: We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates. CONCLUSION: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.
Subject(s)
Diabetes Mellitus, Type 2 , Sleep Initiation and Maintenance Disorders , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Sleep Initiation and Maintenance Disorders/genetics , Genome-Wide Association Study , Reproducibility of Results , Risk Factors , Polymorphism, Single Nucleotide , Mendelian Randomization AnalysisABSTRACT
OBJECTIVE: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). METHODS: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. RESULTS: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 µg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 µg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. CONCLUSION: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.
Subject(s)
Particulate Matter , Receptor, Melatonin, MT2 , Triglycerides , Humans , Female , Male , Middle Aged , Receptor, Melatonin, MT2/genetics , Triglycerides/blood , Blood Glucose , Environmental Exposure/adverse effects , Air Pollutants , Gene-Environment Interaction , China , Polymorphism, Single Nucleotide , Ischemic Stroke/genetics , Ischemic Stroke/blood , Genotype , Air Pollution/adverse effectsABSTRACT
Background: Aspiration pneumonia (AP) is difficult to diagnose and has poor outcomes. This case-control study aimed to explore the risk factors and delineate the antibiotic usage for AP. Methods: Inpatients diagnosed with community-acquired pneumonia (CAP) from 2013 to 2017, enrolled in the urban employee basic medical insurance program in Beijing, were included and classified into the AP (N = 2,885) and non-AP (N = 53,825) groups. Risk factors were identified by logistic regression. Results: Older age (compared to 18-64 years, OR for 65-79 years: 4.3, 95% CI: 3.8-4.9; OR for >80 years: 6.3, 95% CI: 5.6-7.2), male (OR: 1.4, 95% CI: 1.3-1.5), cerebrovascular disease (OR: 3.1, 95% CI: 2.8-3.5), dementia (OR: 2.0, 95% CI: 1.8-2.1), vomiting (OR: 1.4, 95% CI: 1.2-1.7), Parkinson's disease (OR: 2.1, 95% CI: 1.8-2.4), and epilepsy (OR: 3.2, 95% CI: 2.8-3.7) were associated with an increased risk of AP. 92.8% of the AP patients received antibiotic therapy. Among them, patients treated with broad-spectrum antibiotics, antibiotics for injection, and combined antibiotics accounted for 93.3%, 97.9%, and 81.7%, respectively. Conclusions: Older age, male, and several comorbidities were independent risk factors for AP, and combined antibiotics treatments are common, which merits attention in accurate detection of AP in a high-risk population.
Subject(s)
Community-Acquired Infections , Pneumonia , Humans , Male , Case-Control Studies , Pneumonia/drug therapy , Pneumonia/epidemiology , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Risk Factors , Retrospective StudiesABSTRACT
BACKGROUND: Adverse childhood experiences (ACEs) affect children's development, and their harm to health is pervasive throughout the life course. AIMS: To identify ACEs and their risk factors in Chinese household with or without parental mental illness. METHODS: A controlled study was conducted among 181 young adults with parental mental illness (positive group) and 201 demographically matched individuals without parental mental illness (negative group). Univariate and multivariate analyses were performed to study the correlation between ACEs and their risk factors. RESULTS: The positive group suffered emotional abuse, domestic violence, bullying, and cumulative ACEs more frequently than the negative group. In the positive group, living in rural areas and having a low household economic status during childhood were identified as risk factors for cumulative ACEs, whereas a higher education level of the mother was a protective factor for cumulative ACEs in univariate analyses. Low household economic status remained an independent risk factor for cumulative ACEs in the positive group in multivariate analyses. CONCLUSIONS: Children living with parental mental illness are more vulnerable to ACEs, and our findings highlight the importance of socioeconomic factors in increasing the risk of ACEs. To alleviate the deleterious impact of parental mental illness on offspring, multidimensional supports are needed.
Subject(s)
Adverse Childhood Experiences , Mental Disorders , Child , Young Adult , Humans , Parents , Research Design , China/epidemiology , Mental Disorders/epidemiologyABSTRACT
Evidence of the effects of genetic risk score (GRS) on secondary prevention is scarce and mixed. We investigated whether coronary artery disease (CAD) susceptible loci can be used to predict the risk of major adverse cardiovascular events (MACEs) in a cohort with acute coronary syndromes (ACSs). A total of 1667 patients hospitalized with ACS were enrolled and prospectively followed for a median of 2 years. We constructed a weighted GRS comprising 79 CAD risk variants and investigated the association between GRS and MACE using a multivariable cox proportional hazard regression model. The incremental value of adding GRS into the prediction model was assessed by integrated discrimination improvement (IDI) and decision curve analysis (DCA). In the age- and sex-adjusted model, each increase in standard deviation in the GRS was associated with a 33% increased risk of MACE (hazard ratio: 1.33; 95% confidence interval: 1.10-1.61; P = 0.003), with this association not attenuating after further adjustment for traditional cardiovascular risk factors. The addition of GRS to a prediction model of seven clinical risk factors and EPICOR prognostic model slightly improved risk stratification for MACE as calculated by IDI (+1.7%, P = 0.006; +0.3%, P = 0.024, respectively). DCA demonstrated positive net benefits by adding GRS to other models. GRS was associated with MACE after multivariable adjustment in a cohort comprising Chinese ACS patients. Future studies are needed to validate our results and further evaluate the predictive value of GRS in secondary prevention.
Subject(s)
Asian People/genetics , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Genetic Markers , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Aged , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Recurrence , Risk Assessment , Risk Factors , Survival RateABSTRACT
Metformin is the first-choice oral anti-hyperglycemic drug for type 2 diabetes mellitus (T2DM) patients. There are controversies about the association of SLC22A1 rs622342, which was not reported in the Chinese population, and ataxia-telangiectasia mutated (ATM) rs11212617 polymorphisms with metformin efficacy in T2DM. Our study was to investigate the effects of the two single nucleotide polymorphisms on the efficacy of metformin in T2DM of Han nationality in Chaoshan China. After enrollment, 82 newly diagnosed T2DM patients went on 2-month metformin monotherapy. According to BMI before treatment, the patients were divided into a normal weight group (≥18.5 and <25 kg/m2) and an overweight group (BMI ≥ 25 and <30 kg/m2). T-test, Pearson χ2 test, and regression analysis, which adjusted for age, BMI, sex, the dose of metformin, education, tea drink, smoking, and sweet, were used to evaluate the effects of rs622342 and rs11212617 on several variables, such as fasting plasma glucose (FPG). Compared with the AA or CC genotype, patients with AC genotype of rs622342 achieved greater reduction in Δ60FPG and Δ(60-30)FPG (P = 0.00820, 0.00089, respectively). For 11212617, the reduction in Δ30FPG and Δ60FPG was significantly different among patients with the AC genotype (P = 0.00026, 0.00820, respectively). Our results indicated that common variants of SLC22A1 rs622342 and ATM rs11212617 were associated with the efficacy of metformin in T2DM of Han nationality in Chaoshan China.
Subject(s)
Ataxia Telangiectasia , Diabetes Mellitus, Type 2 , Metformin , Ataxia Telangiectasia Mutated Proteins/genetics , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Polymorphism, Single Nucleotide/geneticsABSTRACT
BACKGROUND: Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D. METHOD: A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets. RESULTS: We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × [Formula: see text]). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × [Formula: see text]). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy). CONCLUSION: The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.
Subject(s)
Coronary Disease , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease , Gene Regulatory Networks , Polymorphism, Single Nucleotide , Coronary Disease/diagnosis , Coronary Disease/epidemiology , Coronary Disease/geneticsABSTRACT
We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of "missing heritability" of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of "missing heritability" of type 2 diabetes.
Subject(s)
Alcohol Drinking/epidemiology , Alcohol Drinking/genetics , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease/genetics , Comorbidity , Diabetes Mellitus, Type 2/blood , Genome-Wide Association Study , Humans , Models, Genetic , Phenotype , Polymorphism, Single Nucleotide , Protein Interaction Maps/geneticsABSTRACT
AIM: To identify risk variants associated with gene expression in peripheral blood and to identify genes whose expression change may contribute to the susceptibility to periodontitis. MATERIAL AND METHODS: We systematically integrated the genetic associations from a recent large-scale periodontitis GWAS and blood expression quantitative trait loci (eQTL) data using Sherlock, a Bayesian statistical framework. We then validated the potential causal genes in independent gene expression data sets. Gene co-expression analysis was used to explore the functional relationship for the identified causal genes. RESULTS: Sherlock analysis identified 10 genes (rs7403881 for MT1L, rs12459542 for SIGLEC5, rs12459542 for SIGLEC14, rs6680386 for S100A12, rs10489524 for TRIM33, rs11962642 for HIST1H3E, rs2814770 for AIM2, rs7593959 for FASTKD2, rs10416904 for PKN1, and rs10508204 for WDR37) whose expression may influence periodontitis. Among these genes, AIM2 was consistent significantly upregulated in periodontium of periodontitis patients across four data sets. The cis-eQTL (rs2814770, ~16 kb upstream of AIM2) showed significant association with AIM2 (p = 6.63 × 10-6 ) and suggestive association with periodontitis (p = 7.52 × 10-4 ). We also validated the significant association between rs2814770 and AIM2 expression in independent expression data set. Pathway analysis revealed that genes co-expressed with AIM2 were significantly enriched in immune- and inflammation-related pathways. CONCLUSION: Our findings implicate that AIM2 is a susceptibility gene, expression of which in gingiva may influence periodontitis risk. Further functional investigation of AIM2 may provide new insight for periodontitis pathogenesis.
Subject(s)
Genome-Wide Association Study , Periodontitis , Antigens, CD , Antigens, Differentiation, Myelomonocytic , Bayes Theorem , DNA-Binding Proteins , Genetic Predisposition to Disease/genetics , Humans , Lectins , Periodontitis/genetics , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci/genetics , Receptors, Cell Surface , Transcription FactorsABSTRACT
BACKGROUND: Accumulating evidence has shown that type 2 diabetes (T2D) and coronary artery disease (CAD) may stem from a 'common soil'. The aim of our study was to examine the association between genetic predisposition to T2D and the risk of severe CAD among patients with acute coronary syndromes (ACS) undergoing angiography. METHODS: The current case-control study included 1414 ACS patients with at least one major epicardial vessel stenosis > 50% enrolled in the ACS Genetic Study. The severity of CAD was quantified by the number of coronary arteries involved. Genetic risk score (GRS) was calculated using 41 common variants that robustly associated with increased risk of T2D in East Asians. Logistic regression models were used to estimate the association between GRS and the severity of CAD. RESULTS: In the age-, sex- and BMI-adjusted model, each additional risk allele was associated with a 6% increased risk of multi-vessel disease (OR = 1.06, 95% CI 1.02-1.09). The OR was 1.43 (95% CI 1.08-1.89) for the risk of severe CAD when comparing the extreme tertiles of T2D-GRS. The association was not reduced after further adjustment for conventional cardiovascular risk factors. Additional adjustment for T2D status in our regression model attenuated the association by approximately one quarter. In subgroup analysis, the strengths of the associations between GRS and the severity of CAD were broadly similar in terms of baseline demographic information and disease characteristics. CONCLUSIONS: Our data indicated that genetic predisposition to T2D is associated with elevated risk of severe CAD. This association revealed a possible causal relationship and is partially mediated through diabetic status.
Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide , Acute Coronary Syndrome/epidemiology , Aged , Case-Control Studies , China/epidemiology , Coronary Artery Disease/epidemiology , Coronary Stenosis/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Mendelian Randomization Analysis , Middle Aged , Models, Genetic , Predictive Value of Tests , Prevalence , Prospective Studies , Risk Assessment , Risk Factors , Severity of Illness IndexABSTRACT
BACKGROUND: The relationship between particle matters (PMs) and cardiac arrhythmia has been investigated in numerous studies. However, evidence from developing countries is limited. The aim of this study was to evaluate the association between ambient PMs and hospital admissions for cardiac arrhythmia in China and to examine the potential effect modifiers. METHODS: A time-stratified case-crossover analysis was conducted in 26 large Chinese cities. In total, we identified 175,265 hospital admissions for cardiac arrhythmia between January 2014 and December 2015 from electronic hospitalization summary reports. Conditional logistic regression was performed to estimate the percentage changes in cardiac arrhythmia admissions in relation to interquartile range increases in air pollutants. Age, gender and prespecified comorbid health conditions including hypertension, diabetes, congestive heart failure and hyperlipidemia were stratified to evaluate susceptibility factors. RESULTS: PMs levels were positively associated with the number of hospital admissions for cardiac arrhythmia. Both PM2.5 and PM10 had the strongest impact on lag 2 days. An interquartile range increase in PM2.5 (47.5 µg/m3) and PM10 (76.9 µg/m3) concentrations on lag 2 days was associated with increments of 2.09% (95%CI, 1.58-2.60%) and 2.33% (95%CI, 1.68-2.97%) in hospital admission for cardiac arrhythmia, respectively. Evidence of effect modification by age and comorbid diabetes was observed. The elderly (> 65 years) and patients with comorbid diabetes were more likely to be hospitalized for cardiac arrhythmia following exposure to high levels of PMs. CONCLUSIONS: This study found an increased risk of arrhythmia admissions associated with PM2.5 and PM10 levels among 26 Chinese cities. The associations of PMs with arrhythmia admissions were stronger in aged population and people with diabetes.
Subject(s)
Air Pollutants/adverse effects , Arrhythmias, Cardiac/epidemiology , Environmental Exposure/adverse effects , Hospitalization/statistics & numerical data , Particulate Matter/adverse effects , Aged , Arrhythmias, Cardiac/chemically induced , China/epidemiology , Cities , Comorbidity , Cross-Over Studies , Diabetes Mellitus/epidemiology , Female , Heart Failure/epidemiology , Humans , Hyperlipidemias/epidemiology , Hypertension/epidemiology , Incidence , Logistic Models , Male , Middle AgedABSTRACT
BACKGROUND: Cervical spondylosis adversely affects life quality for its heavy disease burden. The report on the community-based prevalence and associated factors of cervical spondylosis is rare, especially in Chinese population. Whether prevention is needed and how to prevent it is not clear. This study aims to explore its prevalence and related lifestyle factors and provide evidence on prevention of cervical spondylosis. METHODS: A community-based multistage cross-sectional survey of six communities from the Chinese population was conducted. A face-to-face interview was conducted to obtain individual information, and prevalence was calculated. Single-factor analysis and multivariable logistic regressions were used to explore the associated factors in total and subgroup populations. RESULTS: A total of 3859 adults were analyzed. The prevalence of cervical spondylosis was 13.76%, although it differed significantly among the urban, suburban, and rural populations (13.07%, 15.97%, and 12.25%, respectively). Moreover, it was higher in females than in males (16.51% vs 10.49%). The prevalence among different age groups had an inverted U shape. The highest prevalence was in the age group from 45 to 60 years old. The associated factors differed by subgroups. There were positive associations between engaging in mental work, high housework intensity, and sleep duration of less than 7 h/day with cervical spondylosis. Going to work on foot was a negative factor of cervical spondylosis in the total population. For people aged less than 30 years, keeping the same work posture for 1-2.9 h/day was a special related factor. Exposure to vibration was an associated factor for females aged 45-60 years. Menopause was a special related factor for women. CONCLUSIONS: Prevalence of cervical spondylosis was high in Chinese population. People younger than 60 years were the focus of prevention for cervical spondylosis. Moreover, the characters between male and female and among different age groups were different and required targeted interventions.
Subject(s)
Cervical Vertebrae , Life Style , Spondylosis/epidemiology , Adult , Age Distribution , Cervical Vertebrae/diagnostic imaging , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors , Rural Health , Sex Distribution , Spondylosis/diagnostic imaging , Suburban Health , Urban HealthABSTRACT
BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. METHODS: To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection. CONCLUSION: Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC.