Reconstructed influenza A/H3N2 infection histories reveal variation in incidence and antibody dynamics over the life course.

Humans experience many influenza infections over their lives, resulting in complex and varied immunological histories. Although experimental and quantitative analyses have improved our understanding of the immunological processes defining an individual's antibody repertoire, how these within-host processes are linked to population-level influenza epidemiology remains unclear. Here, we used a multi-level mathematical model to jointly infer antibody dynamics and individual-level lifetime influenza A/H3N2 infection histories for 1,130 individuals in Guangzhou, China, using 67,683 haemagglutination inhibition (HI) assay measurements against 20 A/H3N2 strains from repeat serum samples collected between 2009 and 2015. These estimated infection histories allowed us to reconstruct historical seasonal influenza patterns and to investigate how influenza incidence varies over time, space and age in this population. We estimated median annual influenza infection rates to be approximately 18% from 1968 to 2015, but with substantial variation between years. 88% of individuals were estimated to have been infected at least once during the study period (2009-2015), and 20% were estimated to have three or more infections in that time. We inferred decreasing infection rates with increasing age, and found that annual attack rates were highly correlated across all locations, regardless of their distance, suggesting that age has a stronger impact than fine-scale spatial effects in determining an individual's antibody profile. Finally, we reconstructed each individual's expected antibody profile over their lifetime and inferred an age-stratified relationship between probability of infection and HI titre. Our analyses show how multi-strain serological panels provide rich information on long term, epidemiological trends, within-host processes and immunity when analyzed using appropriate inference methods, and adds to our understanding of the life course epidemiology of influenza A/H3N2.

Association of Cantonese dietary patterns with mortality risk in older Chinese: a 16-year follow-up of a Guangzhou Biobank cohort study.

Background: Evidence about the associations between Cantonese dietary patterns and mortality is scarce. We examined the prospective association of the dietary pattern with all-cause, cancer and cardiovascular disease (CVD) mortality in older Chinese. Methods: We included 19 598 participants of a Guangzhou Biobank cohort study aged 50+ years, who were recruited from 2003 to 2006 and followed up until July, 2022. The diet was assessed by using a 300-item validated food frequency questionnaire. The food items were collapsed into 27 food groups. Factor analysis (FA) was used to identify dietary patterns. Multivariable Cox regression produced hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: During 305 410 person-years, 4966 deaths including 1971 CVD, 1565 cancer and 1436 other-causes occurred. Four dietary patterns were identified by FA. No association of the vegetable-based dietary pattern with all-cause, CVD and cancer mortality was found. Compared with the lowest quartile of the healthy Cantonese dietary pattern score, the highest quartile showed lower risks of all-cause (HR 0.86, 95% CI 0.80-0.94) and CVD mortality (HR 0.84, 95% CI 0.72-0.97). The highest quartile of the nut and fruit dietary pattern showed lower risks of all-cause (HR 0.92, 95% CI 0.85-0.99) and CVD mortality (HR 0.82, 95% CI 0.72-0.93), while the unhealthy western dietary pattern was associated with a higher risk of all-cause (HR 1.10, 95% CI 1.01-1.19) and cerebrovascular disease mortality (HR 1.28, 95% CI 1.03-1.58). Conclusion: We have first identified four dietary patterns based on the Cantonese cuisine and found that healthy Cantonese and nut and fruit dietary patterns were associated with lower risks of all-cause and CVD mortality, whereas the unhealthy western dietary pattern was associated with a higher risk of all-cause and cerebrovascular disease mortality.

Associations of soy product intake with all-cause, cardiovascular disease and cancer mortality: Guangzhou Biobank Cohort Study and updated meta-analyses.

PURPOSE: We examined the associations of soy product intake with all-cause, cardiovascular disease (CVD), and cancer mortality and mediations through CVD risk factors based on the Guangzhou Biobank Cohort Study (GBCS), and conducted updated meta-analyses. METHODS: A total of 29,825 participants aged 50 + years were included. Causes of death were identified through record linkage. Soy product intake was assessed by food frequency questionnaire. Cox proportional hazards regression was used to analyze the associations between soy product intake and mortality, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses with CVD risk factors as mediators, and updated meta-analyses were conducted. RESULTS: During 454,689 person-years of follow-up, 6899 deaths occurred, including 2694 CVD and 2236 cancer. Participants who consumed soy product of 1-6 portions/week, versus no consumption, had significantly lower risks of all-cause and CVD mortality (adjusted HR (95% CI) 0.91 (0.86, 0.97) and 0.87 (0.79, 0.96), respectively). In participants who consumed soy product of ≥ 7 portions/week, the association of higher intake with lower CVD mortality was modestly mediated by total cholesterol (4.2%, 95% CI 1.0-16.6%). Updated meta-analyses showed that the highest level of soy product intake, versus the lowest, was associated with lower risks of all-cause and CVD mortality (pooled HR (95% CI) 0.92 (0.88, 0.96) and 0.92 (0.87, 0.98), respectively). CONCLUSION: Moderate and high soy product intake were associated with lower risks of all-cause and CVD mortality. Our findings provide support for current dietary guidelines recommending moderate soy product intake, and contribute additional evidence regarding the potential protective effects of high soy product intake.

Association of adverse childhood experiences with anemia in older Chinese: Guangzhou Biobank Cohort Study.

To examine the association of adverse childhood experiences (ACEs) with anemia among older people. 24,116 participants aged 50 years or above were recruited. Multivariable linear and logistic regression was used to assess the associations of self-reported ACEs number with hemoglobin concentrations (g/dL) and presence of anemia. Older individuals with two or more ACEs, versus no ACEs, showed lower hemoglobin concentrations (ß = - 0.08 g/dL, 95% confidence intervals (CI) - 0.12 to - 0.03) and higher odds of anemia (odds ratio = 1.26, 95% CI 1.01-1.59). A more pronounced association between ACEs and anemia in the lower education group was found, while the association became non-significant in those with higher education (P for ACEs-education interaction = 0.02). ACEs was associated with anemia in older people, and the association was stronger in those with lower education, highlighting the significance of early-life psychological stressors assessment and consideration of education background in geriatric care.

Association of Testosterone and Sex Hormone-Binding Globulin With All-Cause and Cardiovascular Disease Mortality in Older Chinese Men.

BACKGROUND: The associations of high and low testosterone with all-cause and cardiovascular disease (CVD) mortality risk in men are conflicting. Our objective was to examine associations of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin (SHBG) with all-cause and CVD mortality in older Chinese men. METHODS: Total testosterone and SHBG were assayed, and free testosterone and bioavailable testosterone were calculated using Vermeulen formula. Cox proportional hazards regression was used to assess the associations with risks of all-cause and CVD mortality, giving hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Of 3 948 men aged 50+ years, 949 deaths (312 CVD) occurred during an average 10.5-year follow-up. After multivariable adjustments, the highest, versus the third, quartile of total testosterone and free testosterone were associated with higher all-cause mortality risk (1.17 [0.97-1.41] and 1.45 [1.20-1.74], respectively), whereas free testosterone was associated with higher CVD mortality risk (1.88 [1.33-2.66]). Similar positive associations were found for bioavailable testosterone and all-cause mortality risk (1.27 [1.05-1.54]). Lower SHBG (quartile 1 vs quartile 3) was associated with higher all-cause and CVD mortality risk (1.25 [1.04-1.52] and 1.28 [1.08-1.52], respectively). Consistent associations were observed in relatively healthy men and men excluded death during the first year. CONCLUSIONS: Higher total testosterone, free testosterone, and bioavailable testosterone were associated with higher all-cause mortality in older men, higher free testosterone was associated with higher CVD mortality whilst lower SHBG was associated with higher all-cause and CVD mortality. Clarification and confirmation of causality require further mechanistic studies.

Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis.

BACKGRUOUND: Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis. METHODS: Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk. RESULTS: During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies. CONCLUSION: Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Association of insulin resistance and glycemic measures with major abnormal electrocardiogram in older Chinese: Cross-sectional analysis based on the Guangzhou Biobank Cohort study.

AIMS: To examine whether insulin resistance (IR) and glycemic measures were associated with major abnormal electrocardiogram (MA-ECG) and its specific abnormalities in the general population. METHODS: Twelve-lead ECG measurements were performed on 21,720 participants without cardiovascular disease (5,918 men) from the Guangzhou Biobank Cohort Study. The participants were aged 50 years or above (mean age 61.6, standard deviation 7.1 years). Logistic regression was used to assess the associations of IR and glycemic measures with MA-ECG and specific abnormalities. RESULTS: Ln-fasting insulin was significantly associated with MA-ECG and ST-T abnormalities (adjusted odds ratio = 1.52, 95 % confidence interval = 1.15-2.02 and 1.83, 1.37-2.45, respectively, for per standard deviation), which were stronger than those of TyG index with MA-ECG (1.08, 1.04-1.13) and ST-T abnormalities (1.16, 1.11-1.22). Ln-fasting insulin had association with Q wave abnormalities (3.19, 1.52-6.67). The association of TyG index with prolonged QTc varied by sex and obesity (P for interaction ≤ 0.01). Participants with diabetes had stronger associations of ln-fasting plasma glucose with ECG abnormalities than those without. CONCLUSIONS: IR and glycemic measures were associated with MA-ECG, ischemia and prolonged QTc in older Chinese, especially in women, those with obesity, and those with diabetes. These findings underscore the importance of regular evaluations for these groups.

Associations Between Sleep Traits and Social Isolation: Observational and Bidirectional Mendelian Randomization Study.

Social isolation has been found associated with multiple sleep traits in conventional observational studies. However, whether this association is causal and if so, its direction is uncertain. We analyzed the association between social isolation and multiple sleep traits in 30 430 participants from the Guangzhou Biobank Cohort Study. In bidirectional Mendelian randomization, we used 6, 17, and 11 single nucleotide polymorphisms associated with attendance at sports club/gym, religious group, and pub/social club from the UK Biobank (n = 452 302), respectively, and 152 single nucleotide polymorphisms associated with insomnia from the combination of UK Biobank and 23andme (n = 1 331 010). Observationally in the Guangzhou Biobank Cohort Study, insomnia (yes/no) (beta = 0.12, 95% confidence interval (CI) 0.10-0.16) and poor sleep quality (yes/no) (beta = 0.12, CI: 0.08-0.15), but not sleep duration and chronotype, were associated with a higher social isolation score (severe social isolation). In bidirectional MR, genetically predicted insomnia decreases the odds of attendance at sports club/gym (beta = 0.98, CI: 0.98-0.99) and religious groups (beta = 0.99, CI: 0.98-0.99), but not pub/social club. However, these 3 types of social activity were not associated with insomnia. Our results support the causal effects of insomnia on social activity. Further clinical investigations into the utility of insomnia treatment in alleviating social isolation are needed.

Association of fish and meat consumption with non-alcoholic fatty liver disease: Guangzhou Biobank Cohort Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Unhealthy dietary habit is one of major risk factors of NAFLD. However, the associations between specific types of fish and meat consumption and NAFLD remain inconclusive. We explored the associations of fish and meat consumption with NAFLD risk in middle-aged and older Chinese. METHODS: We collected information on 1,862 participants aged 50 years or older from Guangzhou Biobank Cohort Study in 2009 to 2010. Fish and meat consumption was assessed using a validated food-frequency questionnaire. NAFLD was diagnosed by ultrasound. Multivariable logistic regression was used to examine the associations of fish and meat consumption with the presence of NAFLD. RESULTS: The average age was 61.0 (standard deviation = 6.5) years for the participants, 50.2% were women, and 37.2% were diagnosed with NAFLD. After adjusting for age, sex, education, family income, occupation, smoking status, drinking status, physical activity and several metabolic traits, compared with 0 serving/week (one serving = 50 g), fatty fish consumption of ≥ 3 servings/week showed higher odds of NAFLD (odds ratio (OR) and 95% confidence interval (CI): 1.64 (1.12, 2.39)). The highest (≥ 11 servings/week of red meat and poultry; ≥ 3 servings/week of processed meat) versus the lowest (0-3 servings/week of red meat and poultry; 0 serving/week of processed meat) consumption of all other types of meats, including red meat, poultry and processed meat, showed no association with NAFLD (1.17 (0.75, 1.81), 1.02 (0.42, 2.50) and 0.85 (0.50, 1.45), respectively). Aquatic and sea food, and red meat had negative indirect effects on NAFLD via systolic blood pressure and/or high-density lipoprotein cholesterol. Processed meat had positive indirect effects on NAFLD via body mass index, waist circumference, fasting plasma glucose and triglycerides. CONCLUSION: High consumption of fatty fish was associated with higher NAFLD risk. Our results, if causal, provide evidence that limiting consumption of fatty fish can be considered as part of NAFLD lifestyle prevention and treatment.

Associations of meat, fish and seafood consumption with kidney function in middle-aged to older Chinese: a cross-sectional study based on the Guangzhou Biobank Cohort Study.

OBJECTIVE: To examine the associations of red meat, poultry, fish and seafood and processed meat consumption with kidney function in middle-aged to older Chinese. DESIGN: A cross-sectional study based on the Guangzhou Biobank Cohort Study. SETTING: Community-based sample. PARTICIPANTS: 9768 participants (2743 men and 7025 women) aged 50+ years. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was estimated glomerular filtration rate (eGFR) derived from the Chinese-specific equation based on the Modification of Diet in Renal Disease (MDRD) equation (c-aGFR). eGFR derived from the original isotope-dilution mass spectrometry-traceable MDRD study equation, and prevalent chronic kidney disease (CKD) defined as c-aGFR<60 mL/min/1.73 m2 were considered the secondary outcomes. RESULTS: After adjusting for sex, age, body mass index, education, occupation, family income, smoking status, alcohol use, physical activity, daily energy intake, self-rated health and chronic disease history (diabetes, hypertension and dyslipidaemia), compared with processed meat consumption of 0-1 portion/week, those who consumed ≥3 portions/week had lower c-aGFR (ß=-2.74 mL/min/1.73 m2, 95% CI=-4.28 to -1.20) and higher risk of prevalent CKD (OR=1.40, 95% CI=1.09 to 1.80, p<0.0125). Regarding fish and seafood consumption, the associations varied by diabetes (p for interaction=0.02). Fish and seafood consumption of ≥11 portions/week, versus 0-3 portions/week, was non-significantly associated with higher c-aGFR (ß=3.62 mL/min/1.73 m2, 95% CI=-0.06 to 7.30) in participants with diabetes, but was associated with lower c-aGFR in normoglycaemic participants (ß=-1.51 mL/min/1.73 m2, 95% CI=-2.81 to -0.20). No significant associations of red meat or poultry consumption with c-aGFR nor prevalent CKD were found. Similar results were found for meat, fish and seafood consumption with eGFR. CONCLUSIONS: Higher processed meat, fish and seafood consumption was associated with lower kidney function in normoglycaemic participants. However, the associations in participants with diabetes warrant further investigation.

Association of perceived stress with memory decline in older Chinese: The Guangzhou Biobank Cohort Study.

BACKGROUND: Previous studies on associations of perceived stress with poor memory performance in older adults showed inconsistent results. We examined the prospective associations of perceived stress with memory decline using data from Guangzhou Biobank Cohort Study (GBCS). METHODS: Perceived stress was measured by the Perceived Stress Scale (PSS) at baseline (2003-2006), with greater scores indicating greater stress. Memory function was measured by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT), with greater scores indicating better performance, at baseline and follow-up (2008-2012) examinations, analyzed as mean annual change in scores. RESULTS: 9656 participants (72 % women) with mean age 61.6 (standard deviation = 6.4) years were included. During an average of 4.4 years of follow-up, after adjusting for confounders, each one-point greater PSS score was associated with mean annual decline in DWRT scores (ß (95 % CI) = -0.005 (-0.008 to -0.002)). Greater Perceived Helplessness (PH) scores, but not Perceived Self-efficacy scores, was associated with greater mean annual decline in DWRT and IWRT scores (ß (95 % CI) = -0.005 (-0.009 to -0.001) and - 0.012 (-0.018 to -0.005), respectively), and similar patterns were observed in five out of seven PH items (ßs from -0.02 to -0.07). Interaction analysis showed that the association of greater PSS with greater decline in DWRT scores was observed only in those with low family income (ß (95 % CI) = -0.08 (-0.13 to -0.04), P for interaction = 0.03). CONCLUSIONS: Greater perceived stress was associated with a greater decline in delayed recall memory, especially in those with low family income.

Quantity and Variety in Fruit and Vegetable Consumption and Mortality in Older Chinese: A 15-year Follow-Up of a Prospective Cohort Study.

BACKGROUND: Independent associations of quantity and variety of fruit and vegetables (FVs) with mortality in older people are still unclear. OBJECTIVES: This study aimed to explore the association between the quantity and variety in FV consumption and mortality in older Chinese. METHODS: A total of 19,597 participants of the Guangzhou Biobank Cohort Study aged >50 y were recruited from 2003 to 2006 and followed up until April 2021. The diet was assessed using a 300-item validated FFQ. Variety as a continuous variable was defined as the number of unique FV items (excluding potatoes, legumes, and fruit juices) intake per week over the past week. The associations of quantity and variety of FVs with mortality were analyzed, and analyses by the color of edible parts was performed. Multivariable Cox regression yielded HRs and 95% CIs. RESULTS: During 286,821 person-year of follow-up, 4385 deaths occurred, including 1678 cardiovascular diseases (CVD), 1450 cancer, and 1257 other causes. Compared with the lowest quintile of variety in FV, the highest quintile was associated with lower risks of all-cause (HR: 0.81; 95% CI: 0.73-0.89) and CVD mortality (HR: 0.79; 95% CI 0.67-0.92). A greater variety of green and white FV intake was associated with lower risks of all-cause and CVD morality, and a greater variety of red/purple FV intake was associated with lower risks of all-cause and cancer mortality. However, the quantity of FV intake showed no association with all-cause, CVD, and cancer mortality. CONCLUSION: Our findings have first showed that the variety, rather than quantity, in FV intake was associated with a lower risk of mortality in older Chinese. Dietary guidelines may recommend increasing the variety in FV intake, especially green, red/purple, and white FVs in older people.

Association of novel and conventional obesity indices with colorectal cancer risk in older Chinese: a 14-year follow-up of the Guangzhou Biobank Cohort Study.

BACKGROUND: Visceral adiposity index (VAI) and a body shape index (ABSI) were newly developed indices for visceral fat mass. Whether they are superior to conventional obesity indices in predicting colorectal cancer (CRC) remains unclear. We examined the associations of VAI and ABSI with CRC risk, and investigated their performance in discriminating CRC risk compared with conventional obesity indices in the Guangzhou Biobank Cohort Study. METHODS: A total of 28,359 participants aged 50 + years without cancer history at baseline (2003-8) were included. CRC were identified from the Guangzhou Cancer Registry. Cox proportional hazards regression was used to assess the association of obesity indices with the CRC risk. Discriminative abilities of obesity indices were assessed using Harrell's C-statistic. RESULTS: During an average follow-up of 13.9 (standard deviation = 3.6) years, 630 incident CRC cases were recorded. After adjusting for potential confounders, the hazard ratio (95% confidence interval) of incident CRC for per standard deviation increment in VAI, ABSI, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) was 1.04 (0.96, 1.12), 1.13 (1.04, 1.22), 1.08 (1.00, 1.17), 1.15 (1.06, 1.24), 1.16 (1.08, 1.25)and 1.13 (1.04, 1.22), respectively. Similar results for colon cancer were found. However, the associations of obesity indices with risk of rectal cancer were non-significant. All obesity indices showed similar discriminative abilities (C-statistics from 0.640 to 0.645), with WHR showing the highest whilst VAI and BMI the lowest. CONCLUSIONS: ABSI, but not VAI, was positively associated with a higher risk of CRC. However, ABSI was not superior to the conventional abdominal obesity indices in predicting CRC.

Persistence of social isolation and mortality: 10-year follow-up of the Guangzhou Biobank Cohort study.

Although social isolation has been associated with higher mortality risk, the associations of persistence of social isolation with mortality are unclear. We investigated the prospective associations of intermittent and persistent social isolation with all-cause and cause-specific mortality, considering the social contact types (face-to-face and non-face-to-face). 30,518 participants were recruited in 2003-2008 initially and 18,104 participants with re-assessed social isolation information in 2008-2012 were followed up to Dec 2019 in Guangzhou Biobank Cohort Study (GBCS). During an average of 9.7 years of follow-up, 2,119 deaths occurred. The isolation at baseline survey, isolation at second survey and persistent isolation were positively associated with all-cause mortality in the minimal adjusted model (adjusted hazard ratio (AHR) =1.24, 95% CI 1.12-1.38, 1.11, 1.00-1.23 and 1.23, 1.05-1.43, respectively). Totally 47.2% of the risk was explained by health status, SEP, and biological, behavioural and psychological factors. Persistent isolation from face-to-face with co-inhabitants, versus no isolation, was associated with higher risks of all-cause (HR=1.40, 1.09-1.81) and CVD (subdistribution hazard ratio (SHR)=1.92, 1.31-2.81) mortality in fully adjusted model. Our study showed that intermittent and persistent isolation were generally associated with higher risks of mortality, and the risks were even higher in those with persistent face-to-face isolation with co-inhabitants.

Obesity indicators as mediators of the association between age at menopause and blood pressure values.

Having a later age at menopause is associated with having a higher blood pressure (BP) value, but the mediation pathways remain unclear. We quantitatively examined the mediation effects of various obesity indicators using baseline data from phase 4 of the Guangzhou Biobank Cohort Study. The product of coefficients approach and bootstrapping procedures were used to assess the mediation effects of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) on the association between age at menopause and BP values. Age, education, occupation, family income, smoking, drinking, diet, physical activity, age at menarche, number of births, fasting glucose, triglycerides, and high-density lipoprotein cholesterol were adjusted as covariates. Of 5429 women with natural menopause, the mean age and menopausal age were 60.0 (standard deviation = 5.8) and 50.3 (3.1) years, respectively. The prevalence of hypertension was 29.6%. In women with a menopausal age of ≥50 years, BMI, WC, WHR and WHtR showed significant mediation effects on the positive association between menopausal age and BP. The adjusted proportion (95% confidence interval) of the mediation effects for those variables were 26.04% (10.40-116.82%), 25.92% (10.19-108.57%), 14.11% (3.59-62.78%), and 23.17% (8.70-95.81%), respectively, for systolic BP values and 22.59% (10.72-53.60%), 20.67% (9.83-49.31%), 9.21% (2.73-23.92%), and 17.19% (7.56-41.31%) for diastolic BP values. In women with a menopausal age of <50 years, no significant association between age at menopause and systolic/diastolic BP values was found. In conclusion, obesity indicators showed significant mediating effects on the association between having a later age at menopause and having a higher BP value. Further longitudinal studies with detailed and accurate measurements of metabolic changes after menopause and sufficient follow-up are warranted to confirm these results. We demonstrated obesity indicators showed significant mediating effects on the association between later age at menopause (≥50 years) and higher BP.

Association of Multi-Dimensional Factors with Accelerating Age and Constructing a Healthy Lifestyle Index: Guangzhou Biobank Cohort Study.

INTRODUCTION: Ageing process is influenced by multi-dimensional factors collectively. Previous studies examined association of one separate factor with mortality without considering different manifestations of ageing process. We investigated associations of multi-dimensional factors with accelerating age (AA), a proxy to quantify ageing, in older Chinese. METHODS: 9,831 participants from Guangzhou Biobank Cohort Study were included. Four exposure domains of 15 variables including demographic and socio-economic factors, lifestyle factors, stress across the life course, and common diseases were assessed. AA was calculated based on chronological age and eight biomarkers. Traditional multivariable linear and Bayesian Network (BN) models were used. RESULTS: In both traditional and BN models, male sex, smoking, alcohol use, physical inactivity, greater waist circumference, and body mass index (BMI) were associated with higher AA, with the adjusted ß (95% confidence intervals) being 2.75 (2.40-3.09), 1.31 (0.87-1.76), 1.35 (0.55-2.15), 0.64 (0.40-0.88), 0.09 (0.06-0.11), and 0.13 (0.07-0.19) years, respectively. A Healthy Lifestyle Index (HLI) was constructed including the above lifestyle factors (non-smoking, non-alcohol use, physically active, non-central, and non-general obesity) with a point assigned for each. A higher index indicates healthier lifestyle. Compared with participants with an HLI of 5, those with an HLI of 0-2 had 2.90 (2.48-3.32) years older AA. CONCLUSIONS: Male sex, smoking, alcohol use, physical inactivity, greater waist circumference, and BMI were associated with higher AA by 0.09-2.75 years, suggesting that adopting a healthy lifestyle may alleviate process of phenotypic ageing.

Low-carbohydrate diet score and the risk of stroke in older people: Guangzhou Biobank Cohort Study and meta-analysis of cohort studies.

OBJECTIVES: To our knowledge, evidence regarding the association of a low-carbohydrate diet (LCD) with the risk for stroke is limited. The aim of this study was to examine the association between an LCD and stroke in a population with relatively high-carbohydrate intake and risk for stroke and use a meta-analysis to update the evidence. METHODS: The study included 19 850 participants aged ≥50 y without stroke history at baseline in the Guangzhou Biobank Cohort Study. LCD score was calculated based on the percentage of energy from carbohydrate, protein, and fat (range 0-30 points), with a higher score indicating a lower intake of carbohydrate and a higher intake of fat and protein. RESULTS: During an average follow-up of 13.1 y, 1661 stroke events and deaths occurred, including 1255 ischemic strokes. The second, versus the lowest quartile of animal-based LCD scores, were associated with lower risks for all stoke and ischemic stroke (hazards ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.997, and HR, 0.83; 95% CI, 0.72-0.97). Non-significant associations of plant-based or total LCD scores with the risk for stoke were found. CONCLUSIONS: In a population consuming high levels of carbohydrates and low levels of protein and fat, a moderate level of animal-based LCD, but not plant-based LCD, was associated with a lower risk for stroke.

Mendelian randomization on the association of obesity with vitamin D: Guangzhou Biobank Cohort Study.

BACKGROUND: Mendelian randomization (MR) analyses from the West provide evidence that obesity causes lower 25-hydroxyvitamin D [25(OH)D]. As Asian populations are prone to metabolic disorders at a lower body mass index (BMI), whether the association remains in Asian is unclear. We studied whether obesity causes vitamin D deficiency using MR analysis in Chinese. METHODS: We used data from the Guangzhou Biobank Cohort Study. A genetic score including seven BMI-related single-nucleotide polymorphisms (n = 15,249) was used as the instrumental variable (IV) for BMI. Two-stage least square regression and conventional multivariable linear regression in 2,036 participants with vitamin D data were used to analyze association of BMI with vitamin D. RESULTS: Proportion of variation explained by the genetic score was 0.7% and the first stage F-statistic for MR analysis was 103. MR analyses showed that each 1 kg/m2 higher BMI was associated with lower 25(OH)D by -2.35 (95% confidence interval (CI) -4.68 to -0.02) nmol/L. In conventional multivariable linear regression, higher BMI was also associated with lower 25(OH)D (ß = -0.26 nmol/L per 1 kg/m2 increase in BMI, 95% CI -0.46 to -0.06). Sensitivity analyses using two-sample IV analysis and leave-one-out method showed similar results. CONCLUSION: We have first shown by MR and conventional multivariable linear regression that higher BMI causes vitamin D deficiency in Chinese. Our findings highlight the importance of weight control and suggest that vitamin D supplementation may be needed in individuals with overweight or obesity.

Cereal intake and mortality in older Chinese: a 15-year follow-up of a prospective cohort study.

PURPOSE: We examined the association between whole grain and refined grain intake with all-cause, cancer and cardiovascular disease (CVD) mortality using the data from the Guangzhou Biobank Cohort Study. METHODS: 19,597 participants aged 50+ years were recruited from 2003 to 2006 and followed-up until April 2021. Multivariable Cox regression was used to calculate hazard radios (HRs) and 95% confidence intervals (CIs). Substitution analysis was used to replace a serving (50 g/day) of whole grain with a serving of refined grain. RESULTS: During 286,821 person-years of follow-up, 4385 deaths occurred, including 1450 from cancer, 1678 from CVD and 1257 from other causes. Compared with never whole grain intake, the highest intake category of whole grain (> 300 g/week) was associated with lower risk of all-cause (HR 0.90, 95% CI 0.82-0.98) and CVD mortality (HR 0.85, 0.74-0.98). Compared with the low-intake category of refined grain (< 500 g/day), the highest intake category (> 900 g/week) was associated with a lower risk of cancer mortality (HR 0.76, 0.62-0.95), but a higher risk of CVD mortality (HR 1.25, 1.03-1.51). No significant associations were found between whole grain intake and cancer mortality nor refined grain and all-cause mortality. The HRs of all-cause, cancer and CVD mortality substituting a serving of whole grain for refined grain were 0.96 (0.94-0.99), 1.01 (0.99-1.02) and 0.95 (0.90-0.99), respectively. CONCLUSION: We have first shown that in older Chinese, whole grain intake was associated with lower risk of all-cause and CVD mortality. Our results suggest that intake of whole grain of at least 300 g/week and refined grain of ≤ 900 g/day might be suitable for older Asian. Substituting 50 g/day of whole grain for refined grain was associated with a 4-5% lower risk of all-cause and CVD mortality.

Chronotype and cognitive function: Observational study and bidirectional Mendelian randomization.

Background: Association has been found between chronotype and cognitive function in conventional observational studies but whether this association is causal and if so, its direction, is uncertain. There are also concerns among people with later chronotype that their habits may be detrimental to cognitive function. Methods: We analyzed the association between chronotype (measured as sleep midpoint) and cognitive function (measured by Mini-Mental Status Examination (MMSE) and Delayed Word Recall Test (DWRT)) using multivariable linear regression on 14,582 participants in the Guangzhou biobank cohort study (GBCS) from 2008 to 2012. Using bidirectional Mendelian randomization, we used 207 single nucleotide polymorphisms (SNPs) associated with chronotype from the combination of UK Biobank and 23andMe (n = 697,828), and 127 SNPs associated with cognitive function from the combination of UK Biobank and COGENT consortium (n = 257,841). Findings: Observationally in GBCS, later chronotype was associated with better cognitive function (MMSE scores: ß = 0.14 per hour; 95% confidence interval (CI), 0.09-0.19; DWRT scores: ß = 0.07 per hour; 95% CI, 0.04-0.11). Bidirectional MR showed genetic predisposition to early, versus later, chronotype was not associated with cognitive function using inverse-variance weighted (ß = -0.02; 95% CI, -0.05 to 0.01). However, better cognitive function was associated with decreased odds of early chronotype (UK Biobank: odds ratio = 0.88 per standardized score; 95% CI, 0.83-0.93; 23andMe: 0.87 per standardized score; 95% CI, 0.80-0.95). Interpretation: It is a reassuring finding for adults with later chronotype who may be concerned if such a habit has a negative impact on cognitive function. Funding: The National Natural Science Foundation of China; Natural Science Foundation of Guangdong; The University of Hong Kong Foundation for Educational Development and Research; The Health Medical Research Fund in Hong Kong; The University of Birmingham, UK.