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1.
Addiction ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605583

RESUMO

BACKGROUND AND AIMS: Various smoking behaviors, including smoking initiation, age of initiation, heaviness of smoking, and smoking cessation, have been individually related to the risk of mortality; however, no study has assessed these smoking behaviors jointly in relation to mortality. Our study aimed to measure prospectively the association of panoramic smoking burden (PSB), generated from the four aforementioned smoking behaviors, with all-cause and cause-specific mortality, and measure whether such associations are modified by genetic variations. DESIGN: Prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 360,937 participants aged between 37 and 73 years were enrolled in 2006-2010 and followed up through 2018. MEASUREMENTS: The exposure was PSB, constructed based on four smoking behaviors including smoking initiation, age of initiation, heaviness of smoking, and smoking cessation in a weighted method. A genetically determined PSB was also constructed with smoking-associated single nucleotide polymorphisms (SNPs) and categorized into tertiles. The primary outcomes were all-cause and cause-specific mortality. FINDINGS: We identified 15,968 deaths (9,022 from cancer and 5,092 from cardiovascular disease (CVD)) over a median of 11 years' follow-up. For all-cause mortality, compared with participants with the PSB of zero, the hazard ratios of participants who had a PSB of one, two, three, and four were 1.23 (95% CIs: 1.18-1.29), 1.66 (1.59-1.75), 3.33 (3.17-3.51), and 5.76 (4.66-7.13), respectively. Among participants within each genetic risk category, low and intermediate PSB were associated with 45%~58% reduced risk of all-cause death compared with high PSB. Analysis of population attributable risk percent indicated that 21.9%, 19.1%, and 24.7% of all-cause, cancer- and CVD-specific death could have been avoided if all ever smokers initiated smoking after 18 years old, smoked <20 cigarettes/day, and quit smoking. CONCLUSIONS: Panoramic smoking burden (PSB), based on smoking initiation, age of initiation, heaviness of smoking, and smoking cessation, appears to be associated with all-cause and cause-specific mortality in a gradient manner with increasing PSB independent of other traditional and genetic risk factors.

2.
Elife ; 102021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515027

RESUMO

Background: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.Methods: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10-year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.Results: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR <0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47% decrease to a 118% increase. Mediation analyses revealed 28.5% of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7% (P = 0.003) via systolic blood pressure and 6.4% (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.Conclusions: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and BP-related pathways to CHD risk.Funding: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).

3.
Diabetes Metab ; : 101278, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520837

RESUMO

OBJECTIVES: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DMM) in twins, and further to explore whether genetic and early-life environmental factors account for this association. METHODS: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalised estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM. RESULTS: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96∼3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15∼5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20∼0.41). CONCLUSIONS: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.

4.
Twin Res Hum Genet ; 24(4): 228-233, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542028

RESUMO

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.

6.
Eur Heart J ; 42(34): 3374-3384, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34333624

RESUMO

AIMS: The potential difference in the impacts of lifestyle factors (LFs) on progression from healthy to first cardiometabolic disease (FCMD), subsequently to cardiometabolic multimorbidity (CMM), and further to death is unclear. METHODS AND RESULTS: We used data from the China Kadoorie Biobank of 461 047 adults aged 30-79 free of heart disease, stroke, and diabetes at baseline. Cardiometabolic multimorbidity was defined as the coexistence of two or three CMDs, including ischaemic heart disease (IHD), stroke, and type 2 diabetes (T2D). We used multi-state model to analyse the impacts of high-risk LFs (current smoking or quitting because of illness, current excessive alcohol drinking or quitting, poor diet, physical inactivity, and unhealthy body shape) on the progression of CMD. During a median follow-up of 11.2 years, 87 687 participants developed at least one CMD, 14 164 developed CMM, and 17 541 died afterwards. Five high-risk LFs played crucial but different roles in all transitions from healthy to FCMD, to CMM, and then to death. The hazard ratios (95% confidence intervals) per one-factor increase were 1.20 (1.19, 1.21) and 1.14 (1.11, 1.16) for transitions from healthy to FCMD, and from FCMD to CMM, and 1.21 (1.19, 1.23), 1.12 (1.10, 1.15), and 1.10 (1.06, 1.15) for mortality risk from healthy, FCMD, and CMM, respectively. When we further divided FCMDs into IHD, ischaemic stroke, haemorrhagic stroke, and T2D, we found that LFs played different roles in disease-specific transitions even within the same transition stage. CONCLUSION: Assuming causality exists, our findings emphasize the significance of integrating comprehensive lifestyle interventions into both health management and CMD management.


Assuntos
Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Estilo de Vida , Multimorbidade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
7.
Clin Nutr ; 40(7): 4694-4701, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34237696

RESUMO

BACKGROUND & AIMS: People with a higher genetic risk for obesity are more likely to develop cardiovascular disease (CVD), and healthy plant-based dietary patterns may be associated with decreased risks of obesity and cardiovascular events. We investigated whether adherence to healthy plant-foods-rich dietary patterns might attenuate risks of obesity and related cardiovascular abnormalities for people at genetically higher risk of obesity. METHODS: This study included 121,799 middle-aged adults in UK Biobank who were initially free of metabolic diseases and cancer. We calculated a healthful plant-based diet index (hPDI) based on 17 major food groups as well as a genetic risk score (GRS) for obesity consisting of body mass index (BMI)-associated variants. The incidence of cardiovascular events (myocardial infarction, MI, or stroke) was prospectively followed during a mean (SD) 5.1 (0.9) years. RESULTS: We found significant interactions between GRS and hPDI on adiposity (Pinteraction <0.0001); adherence to hPDI was more strongly associated with lower levels of adiposity among participants with higher GRS than those with lower GRS. Further, we found a similar pattern of GRS-hPDI interactions on untreated hypertension (Pinteraction = 0.0036). When we tested GRS-hPDI interactions on cardiovascular events, adherence to hPDI was more strongly associated with a decreased risk of MI among people with high GRS (above median) than those with low GRS (Pinteraction = 0.006). Among participants with high GRS, high adherence to hPDI (the top tertile of hPDI) was associated with an HR 0.54 (95% CI: 0.39, 0.74) for MI, as compared to low adherence. CONCLUSIONS: Adherence to healthy plant-based dietary patterns significantly attenuated risks of cardiovascular abnormalities for people at genetically higher risk of obesity. Our results support the precision medicine strategies considering genetics and dietary habits to modify cardiovascular health for people at higher risk of genetically determined obesity.

8.
Mayo Clin Proc ; 96(7): 1758-1769, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34218856

RESUMO

OBJECTIVE: To investigate the joint associations of amounts of alcohol consumed and drinking habits with the risks of all-cause mortality and cause-specific mortality. PATIENTS AND METHODS: A total of 316,627 healthy current drinkers, with baseline measurements between March 13, 2006, and October 1, 2010, were included in this study. We newly created a drinking habit score (DHS) according to regular drinking (frequency of alcohol intake ≥3 times/wk) and whether consuming alcohol with meals (yes). RESULTS: During a median follow-up of 8.9 years, we documented 8652 incident cases of all-cause death, including 1702 cases of cardiovascular disease death, 4960 cases of cancer death, and 1990 cases of other-cause death. After adjustment confounders and amount of alcohol consumed, higher DHS was significantly associated with a lower risk of all-cause mortality, cardiovascular disease mortality, cancer mortality, or other-cause mortality (Ptrend<.001, Ptrend=.03, Ptrend<.001, and Ptrend<.001, respectively). We observed that the amount of alcohol consumed have different relationships with the risks of all-cause mortality and cause-specific mortality among participants with distinct drinking habits, grouped by DHS. For example, in the joint analyses, a J-shaped association between the amount of alcohol consumed and all-cause mortality was observed in participants with unfavorable DHS (Pquadratictrend=.02) while the association appeared to be U-shaped in participants with favorable DHS (Pquadratictrend=.003), with lower risks in those consuming greater than or equal to 50 g/wk and less than 300 g/wk. CONCLUSION: Our results indicate that alcohol consumption levels have different relationships with the risk of mortality among current drinkers, depending on their drinking habits.


Assuntos
Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares/mortalidade , Etanol , Neoplasias/mortalidade , Medição de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Causas de Morte , Depressores do Sistema Nervoso Central/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Correlação de Dados , Etanol/metabolismo , Etanol/farmacologia , Feminino , Seguimentos , Hormese , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Mortalidade , Fatores de Proteção , Fatores de Risco , Estados Unidos/epidemiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-34329444

RESUMO

BACKGROUND: Little is known about the effects of lifestyle modification on biological aging in population-based studies of middle-aged and older adults. METHODS: We examined the individual and joint associations of multiple lifestyle factors with accelerated biological aging measured by change in frailty index (FI) over 8 years in a prospective study of Chinese adults. Data were obtained on 24,813 participants in the China Kadoorie Biobank (CKB) on lifestyle factors and frailty status at baseline and at 8 years after baseline. Adherence to healthy lifestyle factors included non-smoking or quitting smoking for reasons other than illness, avoidance of heavy alcohol consumption, daily intake of fruit and vegetables, being physically active, body mass index (BMI) of 18.5-23.9 kg/m 2, and waist-to-hip ratio (WHR) <0.90 (men)/0.85 (women). FI was constructed separately at baseline and resurvey using 25 age- and health-related items. RESULTS: Overall, 8,760 (35.3%) individuals had a worsening frailty status. In multivariable-adjusted logistic regression analyses, adherence to healthy lifestyle was associated with a lower risk of worsening frailty status. Compared with robust participants maintaining 0-1 healthy lifestyle factors, the corresponding OR (95% CI) was 0.93 (0.83-1.03), 0.75 (0.67-0.84), 0.68 (0.60-0.77), and 0.55 (0.46-0.65) for robust participants with 2, 3, 4, and 5-6 healthy lifestyle factors. The decreased risk of frailty status worsening by adherence to healthy lifestyle factors was similar in both middle-aged and older adults, and in both robust and prefrail participants at baseline. CONCLUSIONS: Adherence to a healthy lifestyle may attenuate the rate of change in biological aging in middle-aged and older Chinese adults.

10.
Genome Biol ; 22(1): 194, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187551

RESUMO

BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

11.
JAMA Netw Open ; 4(6): e2115297, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34190994

RESUMO

Importance: Previous studies have shown an association between actual age at menarche and risk of all-cause mortality; however, the results are inconsistent, and no study has analyzed the joint associations between genetic susceptibility and actual age at menarche with the risk of mortality in prospective cohorts. Objectives: To investigate joint associations of actual age and genetically determined age at menarche with risk of all-cause mortality. Design, Setting, and Participants: This prospective cohort study was conducted using data from the UK Biobank population across the United Kingdom from March 13, 2006, to October 1, 2010. A total of 264 546 women aged between 39 and 71 years with actual menarcheal age were included in this study; 246 676 of these women had genetic data available. Actual age at menarche was obtained from the touchscreen questionnaire at recruitment from 2006 to 2010. Genetically determined age at menarche was assessed by a genetic risk score. Statistical analysis was performed from August 22 to December 12, 2019. Exposure: Age at menarche. Main Outcomes and Measures: A multivariable Cox proportional hazards regression model was used to assess associations of actual or genetically determined age at menarche with risk of all-cause mortality. Results: The mean (SD) age of the study population at baseline was 56.4 (8.0) years, and the mean (SD) age at menarche included in the analyses was 13.0 (1.6) years. During a median of 9.0 years (range, 8.3-9.7 years) of follow-up, 7761 deaths were documented among the women with actual age at menarche, and 7054 deaths were documented among the women with genetically determined age at menarche. Both the actual age at menarche and the genetically determined age at menarche showed a U-shaped association with the risk of all-cause mortality (lowest actual age [<12 years] vs reference age [15 years]: hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]; highest actual age [≥16 years] vs reference age [15 years]: HR, 1.17 [95% CI, 1.05-1.31]; P < .001 for quadratic trend; genetic risk score [GRS] of 1 vs reference score [GRS of 4]: HR, 1.10 [95% CI, 1.01-1.19; GRS of 6 vs reference score [GRS of 4]: HR, 1.09 [95% CI, 1.00-1.18]; P = .03 for quadratic trend). Significant interactions were also found between actual age at menarche and genetically determined age at menarche with all-cause mortality (HR of mortality associated with age of menarche <12 year was 1.24 [95% CI, 1.10-1.40] in the GRS of 1 group and 1.44 [95% CI, 1.21-1.72] in the GRS of 6 group; P = .001 for interaction). Women with mismatch of actual age and genetically determined age at menarche had the highest mortality risks; participants with the lowest genetic risk score and the highest age at menarche had an HR of 2.12 (95% CI, 1.58-2.83), and participants with the highest GRS and the lowest age at menarche had an HR of 1.44 (95% CI, 1.21-1.72). Conclusions and Relevance: The results suggest that both actual age and genetically determined age at menarche exhibit U-shaped associations with all-cause mortality. Women with mismatch of actual age and genetically determined age at menarche may have the highest risk of all-cause mortality.

12.
Atherosclerosis ; 328: 52-59, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34091070

RESUMO

BACKGROUND AND AIMS: Little is known about the associations between perinatal exposure to maternal smoking and cardiovascular disease (CVD) incidence in offspring, and whether such associations are modified by adulthood and genetically determined smoking behaviors. METHODS: A total of 414,588 participants without CVD at baseline were included from the UK Biobank in 2006-2010 and followed up through 2018. Cox-proportional hazard models were used to examine the association of perinatal maternal smoking with CVD, and both multiplicative and additive interaction analyses were performed to investigate the modification effects of own smoking behaviors. RESULTS: During a median follow-up of 8.93 years, we observed 10,860 incident CVD events, including 7006 myocardial infarction (MI) and 4147 stroke. We found that perinatal exposure to maternal smoking was associated with increased risks of CVD (HR: 1.10; 95% CI: 1.05-1.14), MI (1.10; 1.05-1.16) and stroke (1.10; 1.03-1.18). In addition, we observed significant interactions between perinatal exposure to maternal smoking and adulthood exposure to own smoking on CVD and MI on both the multiplicative and additive scales (all p < 0.05). The attributable proportions due to additive interaction between perinatal and adulthood exposure to smoking were 14% (9%-19%) for CVD and 16% (10%-22%) for MI, respectively. Perinatal exposure to maternal smoking also showed an interaction with genetically determined smoking on MI (p < 0.05), but no interactions were found on the total CVD and stroke. CONCLUSIONS: Our results indicate that perinatal exposure to maternal smoking is associated with increased risks of CVD events, and such relations are modified by adulthood smoking behaviors.


Assuntos
Doenças Cardiovasculares , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Incidência , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos
13.
Nat Commun ; 12(1): 3987, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183656

RESUMO

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.


Assuntos
Metilação de DNA/genética , Leucócitos/citologia , Lipídeos/sangue , Lipoproteínas HDL/sangue , Adulto , Afro-Americanos , Idoso , Carnitina O-Palmitoiltransferase/genética , Ilhas de CpG/genética , Epigênese Genética , Epigenoma/genética , Epigenômica , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Locos de Características Quantitativas/genética
14.
BMC Cardiovasc Disord ; 21(1): 240, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980183

RESUMO

BACKGROUND: Systemic studies of association of genome-wide DNA methylated sites with cardiovascular disease (CVD) in prospective cohorts are lacking. Our aim was to identify DNA methylation sites associated with the risk of CVD and further investigate their potential predictive value in CVD development for high-risk subjects. METHODS: We performed an epigenome-wide association study (EWAS) to identify CpGs related to CVD development in a Chinese population.We adopted a nested case-control design based on data from China PEACE Million Persons Project. A total of 83 cases who developed CVD events during follow-up and 83 controls who were matched with cases by age, sex, BMI, ethnicity, medications treatment and behavior risk factors were included in the discovery stage. Genome-wide DNA methylation from whole blood was detected using Infinium Human Methylation EPIC Beadchip (850 K). For significant CpGs [FDR(false discovery rate) < 0.005], we further validated in an independent cohort including 38 cases and 38 controls. RESULTS: In discovery set, we identified 8 significant CpGs (FDR < 0.005) associated with the risk of CVD after adjustment for cell components, demographic and cardiac risk factors and the first 5 principal components. Two of these identified CpGs (cg06901278 and cg09306458 in UACA) were replicated in another independent set (p < 0.05). Enrichment analysis in 787 individual genes from 1036 CpGs in discovery set revealed a significant enrichment for anatomical structure homeostasis as well as regulation of vesicle-mediated transport. Receiver operating characteristic (ROC) analysis showed that the model combined 8 CVD-related CpGs with baseline characteristics showed much better predictive effect for CVD occurrence compared with the model with baseline characteristics only [AUC (area under the curve) = 0.967, 95% CI (0.942 - 0.991); AUC = 0.621, 95% CI (0.536 - 0.706); p = 9.716E-15]. CONCLUSIONS: Our study identified the novel CpGs associated with CVD development and revealed their additional predictive power in the risk of CVD for high-risk subjects.

15.
Am J Clin Nutr ; 114(1): 42-48, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33829223

RESUMO

BACKGROUND: SCFAs are involved in regulation of body weight and bone health. OBJECTIVES: We aimed to examine whether genetic variations related to butyrate modified the relation between dietary fiber intake and changes in bone mineral density (BMD) in response to weight-loss dietary interventions. METHODS: In the 2-y Preventing Overweight Using Novel Dietary Strategies trial, 424 participants with BMD measured by DXA scan were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A polygenic score (PGS) was calculated based on 7 genetic variants related to the production of butyrate for 370 of the 424 participants. RESULTS: SCFA PGS significantly modified the association between baseline dietary fiber intake and sex on 2-y changes in whole-body BMD (P-interaction = 0.049 and 0.008). In participants with the highest tertile of SCFA PGS, higher dietary fiber intake was related to a greater increase in BMD (ß:  0.0022; 95% CI: 0.0009, 0.0035; P = 0.002), whereas no such association was found for participants in the lower tertiles. In the lowest tertiles of SCFA PGS, men showed a significant increase in whole-body BMD (ß: 0.0280; 95% CI: 0.0112, 0.0447; P = 0.002) compared with women. In the highest tertile, no significant difference was found for the change in BMD between men and women. CONCLUSIONS: Our data indicate that genetic variants related to butyrate modify the relations of dietary fiber intake and sex with long-term changes in BMD in response to weight-loss diet interventions.


Assuntos
Densidade Óssea/fisiologia , Fibras na Dieta/efeitos adversos , Ácidos Graxos Voláteis/sangue , Sobrepeso/prevenção & controle , Perda de Peso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Twin Res Hum Genet ; 24(1): 14-21, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33900162

RESUMO

The objective of this study was to investigate how different obesity measures link to circulating metabolites, and whether the connections are due to genetic or environmental factors. A cross-sectional analysis was performed on follow-up survey data at the Chinese National Twin Registry (CNTR), which was conducted in four areas of China (Shandong, Jiangsu, Zhejiang and Sichuan) in 2013. The survey collected detailed questionnaire information and conducted physical examinations, fasting blood sampling and untargeted metabolomic measurements among 439 adult twins. Linear regression models and bioinformatics analysis were used to examine the relation of obesity measures, including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with serum metabolite levels and related pathways. A co-twin control study was additionally conducted among 15 obesity-discordant monozygotic (MZ) pairs (intrapair BMI difference >3 kg/m2) to examine any differences in metabolites controlling for genetic factors. Eleven metabolites were associated with BMI, WC and WHR after controlling for genetic and shared environmental factors. Pathway analysis identified pathways such as phenylalanine metabolism, purine metabolism, valine, leucine and isoleucine biosynthesis that were associated with obesity. A wide range of unfavorable alterations in the serum metabolome was associated with obesity. Obesity-discordant twin analysis suggests that these associations are independent of genetic liability.


Assuntos
Obesidade , Gêmeos Monozigóticos , Adulto , Índice de Massa Corporal , China , Estudos Transversais , Humanos , Obesidade/genética , Gêmeos Monozigóticos/genética
17.
Int J Epidemiol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826715

RESUMO

BACKGROUND: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. METHODS: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. RESULTS: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS). CONCLUSION: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

18.
Eur J Nutr ; 60(1): 249-258, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32274554

RESUMO

PURPOSE: Obesity is a heterogeneous condition and distinct adiposity subtypes may differentially affect type 2 diabetes risk. We assessed relations between genetically determined subtypes of adiposity and changes in glycemic traits in a dietary intervention trial. METHODS: The four genetic subtypes of adiposity including waist-hip ratio-increase only (WHRonly+), body mass index-increase only (BMIonly+), WHR-increase and BMI-increase (BMI+WHR+), and WHR-decrease and BMI-increase (BMI+WHR-) were assessed by polygenetic scores (PGSs), calculated based on 159 single nucleotide polymorphisms related to BMI and/or WHR. We examined the associations between the four PGSs and changes in fasting glucose, insulin, ß-cell function (HOMA-B) and insulin resistance (HOMA-IR) in 692 overweight participants (84% white Americans) who were randomly assigned to one of four weight-loss diets in a 2-year intervention trial. RESULTS: Higher BMI+WHR-PGS was associated with a greater decrease in 2-year changes in waist circumference in white participants (P = 0.002). We also found significant interactions between WHRonly+PGS and dietary protein in 2-year changes in fasting glucose and HOMA-B (P = 0.0007 and < 0.0001, respectively). When consuming an average-protein diet, participants with higher WHRonly+PGS showed less increased fasting glucose (ß = - 0.46, P = 0.006) and less reduction in HOMA-B (ß = 0.02, P = 0.005) compared with lower WHRonly+PGS. Conversely, eating high-protein diet was associated with less decreased HOMA-B among individuals with lower than higher WHRonly+PGS (ß = - 0.02, P = 0.006). CONCLUSIONS: Distinct genetically determined adiposity subtypes may differentially modify the effects of weight-loss diets on improving glucose metabolism in white Americans. This trial was registered at clinicaltrials.gov as NCT00072995.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adiposidade , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/genética , Dieta Redutora , Humanos , Obesidade/genética , Perda de Peso
19.
Obesity (Silver Spring) ; 29(1): 204-212, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33277814

RESUMO

OBJECTIVE: The purpose of this study was to estimate the associations of genetically determined maternal blood glucose levels with obesity-related outcomes among children from pregnancies with and without gestational diabetes mellitus (GDM). METHODS: A total of 1,114 mothers with (N = 560) and without (N = 554) GDM and their children were included in the present study. A maternal genetic risk score (GRS) for blood glucose was constructed on the basis of 17 single-nucleotide polymorphisms identified from a recent genome-wide association study. RESULTS: It was found that maternal GRS for blood glucose showed different associations with offspring risk of overweight and obesity, as well as adiposity measures (all P for interaction < 0.05). Among mothers without GDM, genetically determined maternal blood glucose levels were associated with an 89% higher risk of overweight in their children (95% CI: 42%-152% per SD increase in GRS, P = 1.40 × 10-5 ) and a 120% higher risk of obesity (44%-235%, P = 2.61 × 10-4 ) after adjustment for covariates. In addition, higher maternal GRS for blood glucose was associated with children's increased obesity-related traits (all P < 0.05). However, no significant associations were observed among children of mothers with GDM. CONCLUSIONS: This study indicates that GDM status may modify the relation between genetically determined glucose levels and obesity risk among children.

20.
Lancet Public Health ; 5(12): e650-e660, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33271078

RESUMO

BACKGROUND: The fraily index is a useful proxy measure of accelerated biological ageing and in estimating all-cause and cause-specific mortality in older individuals in European and US populations. However, the predictive value of the frailty index in other populations outside of Europe and the USA and in adults younger than 50 years is unknown. We aimed to examine the association between the frailty index and mortality in a population of Chinese adults. METHODS: In this prospective cohort study, we used data from the China Kadoorie Biobank. We included adults aged 30-79 years from ten areas (five urban areas and five rural areas) of China who had no missing values for the items that made up the frailty index. We did not exclude participants on the basis of baseline morbidity status. We calculated the follow-up person-years from the baseline date to either the date of death, loss to follow-up, or Dec 31, 2017, whichever came first, through linkage with the registries of China's Disease Surveillance Points system and local residential records. Active follow-up visits to local communities were done annually for participants who were not linked to any established registries. Causes of death from official death certificates were supplemented, if necessary, by reviewing medical records or doing standard verbal autopsy procedures. The frailty index was calculated using 28 baseline variables, all of which were health status deficits measured by use of questionnaires and physical examination. We defined three categories of frailty status: robust (frailty index ≤0·10), prefrail (frailty index >0·10 to <0·25), and frail (frailty index ≥0·25). The primary outcomes were all-cause mortality and cause-specific mortality in Chinese adults aged 30-79 years. We used a Cox proportional hazards model to estimate the associations between the frailty index and all-cause and cause-specific mortality, adjusting for chronological age, education, and lifestyle factors. FINDINGS: 512 723 participants, recruited between June 25, 2004, and July 15, 2008, were followed up for a median of 10·8 years (IQR 10·2-13·1; total follow-up 5 551 974 person-years). 291 954 (56·9%) people were categorised as robust, 205 075 (40·0%) people were categorised as prefrail, and 15 694 (3·1%) people were categorised as frail. Women aged between 45 years and 79 years had a higher mean frailty index and a higher prevalence of frailty than did men. During follow-up, 49 371 deaths were recorded. After adjustment for established and potential risk factors for death, each 0·1 increment in the frailty index was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1·68, 95% CI 1·66-1·71). Such associations were stronger among younger adults than among older adults (pinteraction<0·0001), with HRs per 0·1 increment of the frailty index of 1·95 (95% CI 1·87-2·03) for those younger than 50 years, 1·80 (1·76-1·83) for those aged 50-64 years, and 1·56 (1·53-1·59) for those 65 years and older. After adjustments, there was no difference between the sexes in the association between the frailty index and all-cause mortality (pinteraction=0·75). For each 0·1 increment of the frailty index, the corresponding HRs for risk of death were 1·89 (95% CI 1·83-1·94) from ischaemic heart disease, 1·84 (1·79-1·89) from cerebrovascular disease, 1·19 (1·16-1·22) from cancer, 2·54 (2·45-2·63) from respiratory disease, 1·78 (1·59-2·00) from infection, and 1·78 (1·73-1·83) from all other causes. INTERPRETATION: The frailty index is associated with all-cause and cause-specific mortality independent of chronological age in younger and older Chinese adults. The identification of younger adults with accelerated ageing by use of surrogate measures could be useful for the prevention of premature death and the extension of healthy active life expectancy. FUNDING: The National Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, the Kadoorie Charitable Foundation, and the Wellcome Trust.


Assuntos
Fragilidade/mortalidade , Adulto , Fatores Etários , Idoso , Causas de Morte , China/epidemiologia , Comorbidade , Feminino , Nível de Saúde , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Características de Residência , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos
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