Introduction:Chronic kidney disease (CKD) is a growing public health concern, yet evidence on its incidence is limited in China. Methods:Using data from the China Kadoorie Biobank (CKB), which recruited 512,723 participants aged 30 to 79 years from 10 areas across China, we analyzed 5 major CKD subtypes: diabetic kidney disease (DKD), hypertensive nephropathy (HTN), glomerulonephritis (GN), chronic tubulointerstitial nephritis (CTIN), and obstructive nephropathy (ON). Total CKD included the aforementioned subtypes, CKD due to other reasons, or chronic kidney failure. Outcomes were ascertained through linkages to local death and disease registries and health insurance databases until December 31, 2018. Poisson regression model was used to assess secular trends and population variations. Results:Over a mean of 9.5 years of follow-up, 5662 total CKD cases were identified. The crude incidence rate (per 100,000 person-years) of total CKD was 119.7 (95% confidence interval: 116.6-122.8) between 2009 and 2018, with an annual increase of 8.9% (7.9%-10.0%) after adjusting for age, sex, and study area. The crude incidence rates were highest in GN, whereas biggest increases were observed in ON, DKD, and HTN. Total CKD incidence rate was similar between urban and rural areas; however, those of different subtypes varied: DKD or CTIN were higher in urban areas, and ON was significantly higher in rural areas. Males, older adults, and participants with hypertension or diabetes mellitus were at higher risks. Conclusion:Despite the underestimation of CKD incidence because of outcome ascertainment methods, the incidence of total CKD and its subtypes increased in the CKB population during 2009 to 2018. Measures should be taken against major driving factors, such as diabetes mellitus, hypertension, and kidney stones.

Gaps exist concerning the associations of PM2.5-10, gaseous pollutants, and composite pollutants with the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The interaction effects of lifestyle factors, indoor air pollution, and meteorological conditions with air pollutants have been underexplored. This time-stratified case-crossover study was nested within the China Kadoorie Biobank cohort study of middle-aged and elderly participants from five urban and five rural areas in China spanning from 2004 to 2018. 10,712 participants were included, each with a mean of 2.3 episodes of AECOPD hospitalizations during the observation period. A composite air pollution score was derived through principal component analysis. Short-term exposure to particulate matter and NO2 was positively associated with hospital admissions for AECOPD, with the largest temperature- and humidity-adjusted odds ratio (95% confidence interval) of 1.101 (1.073, 1.129) at a lag of 1 day for per 1 standard deviation increase in air pollution score. The effect of O3 appeared to be conflicting. The associations were further corroborated by the self-controlled case-series design. Unfavorable body shapes, cold season, and low humidity could exacerbate the influence of air pollution. These findings reinforce the evidence of links between air pollution and AECOPD and implicate the management of body weight and cold and dry circumstances.

BACKGROUND:Evidence linking components of particulate matter with diameters ≤2.5 μm (PM2.5) to the incidence of cardiovascular disease (CVD) remains scarce and inconsistent. OBJECTIVES:The aim of this study was to investigate the associations of long-term exposure to PM2.5 components with incident CVD risk, considering both absolute concentrations and relative proportions. METHODS:This study included 487,037 participants from the China Kadoorie Biobank who were free of CVD or cancer at baseline. Three-year moving average concentrations of PM2.5 and its components (black carbon [BC], organic matter, chloride [Cl-], nitrate [NO3-], sulfate [SO42-], and ammonium [NH4+]) were geocoded to participants at 1 × 1 km resolution according to their community recruitment clinic locations. Time-varying Cox proportional hazards models were used to evaluate the associations between PM2.5 components and incident CVD risk. Substitution models were used to estimate the effects of reallocating PM2.5 component proportions while keeping total PM2.5 mass constant, thereby evaluating changes in CVD risk associated with shifts in component composition. RESULTS:Over a median 15.1-year follow-up, a total of 196,224 CVD cases, including 72,747 of ischemic heart disease, 74,594 of ischemic stroke, 17,553 of hemorrhagic stroke, and 54,306 of other cerebrovascular diseases, were documented. Long-term exposure to PM2.5 components was associated with increased risk for CVD and its major subtypes. For total CVD, the HRs per IQR increase were 1.15 (95% CI: 1.13-1.17) for BC, 1.17 (95% CI: 1.15-1.18) for organic matter, 1.28 (95% CI: 1.25-1.32) for Cl-, 1.29 (95% CI: 1.24-1.33) for NO3-, and 1.23 (95% CI: 1.20-1.25) for SO42-. Higher proportions of Cl-, SO42-, and BC were associated with an increased risk for ischemic stroke, and the aforementioned inorganic ions were also positively associated with ischemic heart disease. Substituting 1% of any other PM2.5 component with Cl- was associated with a 3% to 8% higher risk for total CVD, whereas substitutions with BC were associated with a 1% to 8% higher risk for ischemic stroke, and substitution with SO42- was associated with a 2% to 5% higher risk for ischemic heart disease. CONCLUSIONS:Long-term exposure to PM2.5 chemical components was positively associated with CVD risk. Critically, CVD risk was influence by compositional shifts, with a particularly hazardous profile characterized by higher proportions of Cl-, BC, or SO42-. These findings underscore the importance of implementing targeted, health-oriented control strategies that prioritize specific PM2.5 components.

BACKGROUND:Abdominal adiposity may contribute to both general and cardiovascular ageing, yet the extent to which accelerated biological age (BA) at distinct molecular levels mediates these effects has not been fully elucidated. METHODS:Three BA measures were constructed using metabolomics (MetaboAge, n=4391), clinical biomarkers (Klemera-Doubal method BA; KDM-BA, n=12 369) and DNA methylation (DNAm PhenoAge, n=980) within the prospective China Kadoorie Biobank and their predictive accuracy for all-cause mortality were evaluated. We explored the potential causal effects of abdominal adiposity, measured by waist-to-hip ratio (WHR) and WHR adjusted for body mass index (WHRadjBMI), on BA acceleration using observational study and Mendelian randomisation. We further investigated the extent to which BA accelerations mediated the effects of abdominal adiposity on cardiovascular ageing (assessed by atherosclerotic cardiovascular disease (ASCVD) incidence and mortality) and general ageing (assessed by all-cause mortality and frailty index). RESULTS:Both MetaboAge and KDM-BA improved prediction for all-cause mortality beyond chronological age (area under the receiver operating characteristic curve (AUROC) difference: MetaboAge=0.040, KDM-BA=0.012, p<0.001). In observational analyses, abdominal adiposity was associated with accelerated ageing across all three BA clocks, with effect estimates ranging from 0.055 (95% CI 0.038 to 0.073) for the association between WHR and KDM-BA acceleration to 0.107 (0.044 to 0.170) for the association between WHRadjBMI and DNAm PhenoAge acceleration. These associations remained significant in Mendelian randomisation analyses. Mediation analyses revealed that acceleration of MetaboAge and KDM-BA partially explained the effects of abdominal adiposity on cardiovascular ageing (%mediated: 6.0%-25.3%), while all three BA clocks accelerations mediated associations with general ageing assessed by all-cause mortality (%mediated: 17.6%-60.6%), with MetaboAge contributing the largest proportion of mediation. Additionally, KDM-BA acceleration mediated the association between abdominal adiposity and frailty index. CONCLUSIONS:Abdominal adiposity is associated with ageing acceleration across multiple biological domains, especially via metabolic alterations captured by MetaboAge. Our findings demonstrated that targeting abdominal adiposity-related metabolic dysfunction may mitigate age-related conditions.

Background Breastfeeding may be associated with lower future risk of maternal type 2 diabetes (T2D). However, existing evidence is inconsistent and derived largely from studies in high-income countries. We assess the association of breastfeeding and breastfeeding duration with incident T2D among Chinese women.Research design and methods The prospective China Kadoorie Biobank recruited 512 724 adults from 10 localities across China between 2004 and 2008. During 11.8 years’ follow-up, 12 011 cases of incident T2D were recorded among 283 855 female participants without prior diabetes. Cox regression was used to estimate adjusted HRs for incident T2D associated with ever breastfeeding, mean breastfeeding duration per child and lifetime breastfeeding duration.Results Overall, 98.6% of female participants were parous, among whom 97.2% reported ever breastfeeding, with mean lifetime breastfeeding duration and breastfeeding duration per child of 34.8 and 14.9 months, respectively. Among parous female participants, there was no clear association between ever breastfeeding and risk of incident T2D (adjusted HR 1.06 (95% CI 0.94 to 1.20)). A modest log-linear positive association was observed between lifetime breastfeeding duration and incident T2D among parous female participants who ever breastfed (1.01 (1.01 to 1.02) per 6 months longer breastfeeding), but this was attenuated after adjustment for parity (1.00 (0.99 to 1.01)). Mean breastfeeding duration per child was not associated with incident T2D (1.01 (0.99 to 1.02) per 6 months longer breastfeeding).Conclusions In this population with almost universal childbearing and breastfeeding, there was no apparent association of ever breastfeeding or of breastfeeding duration with incident T2D.

BACKGROUND:Substantial improvements in air quality have been recorded following the implementation of China's Clean Air Act (CCAA) in 2013. However, the association between CCAA implementation and individual-level cardiovascular disease (CVD) risk remains unclear. We aimed to examine the long-term association between CCAA implementation and individual-level predicted CVD risk. METHODS:In this prospective, quasi-experimental study, we used data from the China Kadoorie Biobank, a prospective cohort study that recruited participants from five urban and five rural areas across China between 2004 and 2008, with three resurveys conducted after the baseline survey (in 2008, 2013-14, and 2020-21). We included 34 862 individuals (mean age 51·3 years) who participated in at least one resurvey and had no history of CVD at baseline. Participants were classified into intervention (n=25 497) and control (n=9365) groups based on the local government's targets for particulate matter reduction. We estimated the 10-year risk of incident CVD morbidity or mortality using a validated risk prediction model. We used a difference-in-difference model to assess the long-term association between CCAA implementation and predicted risk, with adjustments made for regional confounders and individual-level characteristics, including demographics, lifestyle factors, medical history, and indoor air pollution exposure. The relationship between changes in long-term exposure to PM2·5, PM10, and O3 and predicted risk after CCAA implementation was analysed using a linear model. The estimated risk differences associated with air pollutant changes were estimated based on the magnitude of changes and their corresponding effect sizes. FINDINGS:After the CCAA was implemented, PM2·5 and PM10 concentrations declined in both groups, but O3 concentrations increased. The intervention group showed a 3·95% (95% CI 3·18-4·72%) lower increase in predicted risk than the control group, with larger estimated differences under stricter enforcement. Between 2013 and 2021, each 10 μg/m3 change in PM2·5 concentration was positively associated with a 1·80 (1·34-2·27) percentage point change in predicted CVD risk, whereas each 10 μg/m3 change in PM10 concentration was associated with a 1·24 (0·84-1·63) percentage point change and each 10 μg/m3 change in O3 concentration with a 0·58 (0·33-0·83) percentage point change. Overall, the observed changes in air pollutants during the study period were associated with an average 6·6 percentage point reduction in predicted CVD risk. INTERPRETATION:The CCAA and improved air quality were associated with a slower increase in predicted CVD risk, supporting the necessity for stricter, multipollutant air quality policies to maximise public health benefits. FUNDING:National Natural Science Foundation of China, Kadoorie Charitable Foundation, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, Chinese Ministry of Science and Technology, and UK Wellcome Trust.

Introduction Chronic kidney disease (CKD) is a growing public health concern, yet evidence on its incidence is limited in China. Methods Using data from the China Kadoorie Biobank (CKB), which recruited 512,723 participants aged 30-79 from 10 areas across China, we analyzed five major CKD subtypes: diabetic kidney disease (DKD), hypertensive nephropathy (HTN), glomerulonephritis (GN), chronic tubulointerstitial nephritis (CTIN), and obstructive nephropathy (ON). Total CKD included the aforementioned subtypes, CKD due to other reasons, or chronic kidney failure. Outcomes were ascertained through linkages to local death and disease registries and health insurance databases until December 31, 2018. Poisson regression model was used to assess secular trends and population variations. Results Over a mean 9.5-year follow-up, 5,662 total CKD cases were identified. The crude incidence rate (per 100,000 person-years) of total CKD was 119.7 (95% CI, 116.6-122.8) between 2009-2018, with an annual increase of 8.9% (7.9%-10.0%) after adjusting for age, sex, and study area. The crude incidence rates were highest in GN, while biggest increases were observed in ON, DKD, and HTN. Total CKD incidence rate was similar between urban and rural areas, but those of different subtypes varied: DKD/CTIN were higher in urban areas, and ON was significantly higher in rural areas. Males, older adults, and participants with hypertension or diabetes were at higher risks. Conclusion Despite the underestimation of CKD incidence due to outcome ascertainment methods, the incidence of total CKD and its subtypes increased in the CKB population during 2009-2018. Measures should be taken against major driven factors, such as diabetes, hypertension, and kidney stones.

Obesity is a well-established risk factor for early death, but the exact shapes of associations between young adulthood body mass index (BMI) and mortality in later life were not well characterised. Using data from the prospective China Kadoorie Biobank study of 430,373 participants (∼57% being women, with a median follow-up duration of 12 years), Cox regression analysis was performed to yield adjusted hazard ratios (HRs) relating BMI at ∼25 years old (BMI25) with different mortality outcomes including total mortality (n = 36,814), cardiovascular mortality (n = 13,620), cancer mortality (n = 13,394) and respiratory mortality (n = 2929). Mean BMI25 of participants was 21.9 (SD = 2.5) kg/m2, and 1.9% participants were obese at young adulthood (i.e., BMI25 ≥28.0 kg/m2). Independent of baseline BMI, higher BMI25 was associated with much higher levels of blood glucose and diabetes prevalence at baseline. After adjusting for potential confounders e.g., age, smoking, and baseline measured BMI, BMI25 had a strong positive log-linear association with all above-mentioned mortality outcomes, those being obese at young adulthood had a HR of 1.85 (95% CI: 1.75-1.95), 1.85 (1.71-2.00), 1.40 (1.26-1.56) and 2.34 (1.96-2.81), respectively, compared with participants having BMI25 of 18.5-20.0 kg/m2. The association with cancer mortality was more pronounced in men than in women, but no such heterogeneity was observed for total, cardiovascular diseases (CVD), and respiratory mortality. To conclude, the observed strong monotonically positive associations between young adulthood BMI and various mortality outcomes, independent of BMI in later life, support the need for early and stringent body weight control to prevent early death.

The transition from work to retirement is a critical shift in an individual's later life. Utilizing retrospective data from the 2014 China Health and Retirement Longitudinal Study (CHARLS), this study employed sequence analysis to identify typical retirement transition patterns, followed by multiple regression analysis to examine their association with physical health. Five groups of retirement trajectories are identified: "Not Retired," "Early Retirement," "Late Retirement from Agricultural Employment," "Statutory Retirement," "Late Retirement from Self-employment". The "Statutory Retirement" and "Early Retirement" groups typically complete their retirement transition earlier, often retiring at the statutory age with substantial pension support. In contrast, the "Not Retired," "Late Retirement from Agricultural Employment," and "Late Retirement from Self-employment" groups exit the labor force later in life. These individuals are primarily engaged in agricultural production or self-employment and generally lack robust pension insurance. Regression analysis found a significant association between retirement transition patterns and physical health. The "Statutory Retirement" group demonstrates lower Instrumental Activity of Daily Living (IADL) (B = -0.393, P < 0.001), and NAGI (B = -0.791, P < 0.001) scores. The "Late Retirement from Self-employment" group also showed lower IADL (B = -0.356, P < 0.01) and NAGI (B = -0.555, P < 0.001) scores. The "Early Retirement" group exhibits a lower NAGI score (B = -0.345, P < 0.001). In contrast, the "Late Retirement from Agricultural Employment" group was associated with higher scores in Activities of Daily Living (ADL) (B = 0.212, P < 0.05) and IADL (B = 0.407, P < 0.01). Contact with children moderated the relationship between retirement transition and physical health. Increased intergenerational contact had a stronger positive correlation with health for individuals in the "Late Retirement from Agricultural Employment" group but showed no significant health benefit for those in the "Statutory Retirement" group.

ABSTRACT Background The health consequences of being underweight are less well‐studied than obesity. We aimed to examine the association between body mass index (BMI) and mortality from a wide range of diseases across the full BMI spectrum, with particular focus on how low BMI may affect premature and nonpremature death. Methods After excluding ever‐smokers and those with pre‐existing major diseases, this study included 262 704 women aged 30–79 from the China Kadoorie Biobank. The baseline BMI (kg/m2) was calculated using measured height and weight and classified into six groups: < 18.5, 18.5–19.9, 20.0–22.4, 22.5–23.9 (reference), 24.0–27.9 and ≥ 28.0. Long‐term follow‐up was conducted by linking to the local death registry. Cox regression was used to estimate the hazard ratios (HRs) of BMI with all‐cause and cause‐specific mortality, after adjusting for waist circumference and potential confounders. Results At baseline, 3.9%, 7.8% and 11.4% of participants had BMIs (kg/m2) of < 18.5, 18.5–19.9 and ≥ 28.0, respectively. During a median follow‐up of 17.1 years, 29 531 deaths were recorded, including 11 455 premature deaths (under the age of 70) and 18 076 nonpremature deaths. The risk of all‐cause mortality significantly increased at the lower extreme of BMI, reached a nadir around 23.5 kg/m2 estimated from restricted cubic splines and showed a modest increase at the upper extreme. Participants with BMI < 18.5, 18.5–19.9 and 20.0–22.4 had higher risks of premature death (HRs) of 1.91 (1.73–2.10), 1.24 (1.14–1.34) and 1.16 (1.11–1.21), respectively. The corresponding HRs for nonpremature death were 1.46 (1.36–1.56), 1.17 (1.10–1.23) and 1.04 (1.01–1.08). The analysis of premature death involved 33 diseases from eight ICD‐10 chapters, and nonpremature death involved 40 diseases from nine chapters. Underweight was linked to an increased risk of premature death in seven chapters and 10 diseases, including neoplasms (HR = 1.36, 95% CI: 1.16–1.59), endocrine‐metabolic (6.03, 4.13–8.82), circulatory (1.85, 1.56–2.20), respiratory (5.85, 3.89–8.80), digestive (5.64, 3.13–10.18), genitourinary (2.61, 1.20–5.69) and external causes (2.06, 1.55–2.72). Underweight was also associated with an increased risk of nonpremature death in four chapters and seven diseases. In contrast, obesity was only associated with increased risks of premature and nonpremature death in two and one chapters, respectively. Conclusion Among Chinese female healthy never‐smokers, underweight was an important risk factor for all‐cause and multiple cause‐specific mortality, especially the risk of premature death. While addressing the global obesity epidemic, the negative health consequences of low weight should not be ignored.

Abstract Copy-number variants (CNVs) represent an important source of genetic variation that can influence complex traits and disease risk by altering gene dosage, disrupting coding sequence, or modifying regulatory elements. Existing CNV association studies have been limited in scale and have largely focused on European-ancestry populations. We present a CNV genome-wide association study of 13 anthropometric and cardiometabolic traits in 94,730 adults from the China Kadoorie Biobank, a large East Asian study. We identify 19 independent locus-phenotype associations across 15 unique loci. Novel associations include random plasma glucose at 8p23.1 (β = -0.29 SD, P = 5.40×10⁻) and 14q11.2 (β = +0.43 SD, P = 8.41×10⁻), diastolic blood pressure at 7p21.1 (β = +0.75 SD, P = 5.25×10⁻), and duplication-associated reductions in body fat percentage at 12p12.1 (β = -0.74 SD, P = 8.11×10⁻) and 17q12 (β = -0.56 SD, P = 7.36×10⁻). We also replicated established dosage-sensitive regions, most prominently at two distinct intervals within 16p11.2 (BP2-BP3 and BP4-BP5), where CNVs show large bidirectional dosage effects across 5 adiposity traits including body mass index (β = -0.84 SD per copy, P = 1.77×10⁻). These findings identify structural variants contributing to cardiometabolic and anthropometric trait variation in Chinese adults and expand the ancestry diversity of CNV association studies.

Background:Exacerbation of COPD (ECOPD) has been linked to increased cardiovascular disease (CVD) risk within the first year, yet longer term risk is unclear. We aimed to investigate the short-term and long-term CVD risks after severe ECOPD. Methods:Patients with self-reported or spirometry-detected COPD at baseline and patients with newly documented COPD during follow-up were included from the China Kadoorie Biobank. Multiple data sources were used to collect information on ECOPD hospitalisation and CVD incidence during follow-up. Time-dependent Cox regression models were used to estimate the hazard ratios and 95% confidence intervals for each risk period following ECOPD compared to the baseline period. Results:Of the 46 514 patients included, 48.2% had screen-detected COPD, 26.2% had self-reported COPD and 25.6% had newly documented COPD. During a median 11-year follow-up, 1185 acute myocardial infarction, 5778 other ischaemic heart disease, 1078 heart failure, 2390 pulmonary heart disease, 4989 ischaemic stroke and 1648 intracerebral haemorrhage cases occurred. Post-ECOPD risks of all outcomes were prominently elevated, with first-week hazard ratios (95% CI) of 8.60 (5.40-13.70), 6.68 (5.16-8.65), 10.98 (6.74-17.89), 24.76 (19.40-31.60), 3.11 (2.16-4.48) and 2.40 (1.27-4.54), respectively. The risks diminished thereafter but could persist for 6 years or longer. All three categories of patients with COPD faced increased risks of most outcomes, with patients with COPD at baseline bearing higher post-ECOPD risks of other ischaemic heart disease and pulmonary heart disease. Conclusion:CVD risks increased considerably after ECOPD, with risks of cardiac diseases and ischaemic stroke increased for 6 years or longer. Patients with screen-detected COPD had a similar burden of ECOPD and subsequent CVD to patients with doctor-diagnosed COPD.

BACKGROUND:Little is known about how sleep problems affect total life expectancy (LE) and LE free of cardiovascular disease (CVD) and its subtypes. METHODS:We included 483384 adults from the China Kadoorie Biobank. Sleep duration was categorized as <6 hours per day (h/d), 6-9 h/d, and >9 h/d. Sleep disturbance was defined as having at least one of the following: self-reported difficulties initiating and maintaining sleep, early morning awakening, and daytime dysfunction. We estimated sex-specific LE with and without CVD at age 40 by using multistate Markov models, with separate models specified for total CVD, ischemic heart disease, ischemic stroke, and hemorrhagic stroke as the disease state. RESULTS:During a median follow-up of 12.1 years, we documented 135429 incident CVD events and 48372 deaths. Longer sleep duration (>9 h/d) had the greatest impact on total LE and LE free of CVD and its subtypes, with the impact on total LE greater than that of disease-free LE. At age 40, total LE and LE without CVD were reduced by 2.11 and 1.29 years in men, and 1.37 and 0.43 years in women, respectively. In contrast, sleep disturbance mainly reduced disease-free LE, reducing the proportion of life spent healthy; compared with those without sleep disturbance, men and women had 0.46 and 0.22 years lower total LE, and 0.99 and 1.05 years lower LE without CVD. CONCLUSIONS:Abnormal sleep duration, especially long sleep, and sleep disturbance were linked with lower total LE and LE free of CVD in this Chinese population, highlighting the importance of good sleep habits.

BACKGROUND:Adiposity is associated with increased risk of breast cancer in post-menopausal women, while the association appears to be the inverse among premenopausal women in Western populations, but is unclear for Chinese women. METHODS:Using data on 284 538 women with no history of cancer, hysterectomy, oophorectomy, or breast surgery at baseline in 2004-8 from the China Kadoorie Biobank (a prospective cohort study), Cox regression was used to estimate adjusted hazard ratios (HRs) for breast cancer and its subtypes by measured body mass index (BMI) and other adiposity measures (waist circumference, fat percentage, waist-hip ratio, fat mass) and by self-reported BMI at age 25 years. RESULTS:Mean BMI was 23.8 (3.5 SD) kg/m2 at baseline (mean age 51.4 years) and 21.9 (2.7 SD) kg/m2 at age 25 years. During 10 years of follow-up, there were 2379 incident breast cancer cases. Higher BMI was associated with a higher risk of breast cancer in women who were post-menopausal [HR = 1.35, 95% confidence interval (CI) 1.24-1.47] and premenopausal (HR = 1.13, 95% CI 1.03-1.24) at baseline, but not when censoring at age 50 years to capture mainly premenopausal cancers. Among post-menopausal women, BMI was associated with oestrogen-receptor positive (ER ) (HR = 1.47, 95% CI 1.24-1.74), but not with oestrogen-receptor negative (ER-) breast cancer (HR = 1.02, 95% CI 0.75-1.37). Waist circumference and fat percentage were associated with a higher risk of breast cancer. CONCLUSION:In this cohort of Chinese women, higher levels of general and central adiposity were associated with a higher risk of breast cancer, in both women who were premenopausal and women who were post-menopausal at baseline. Among post-menopausal women, adiposity was associated with ER   but not ER - breast cancer.

BACKGROUND:Carotid artery intima-media thickness (cIMT) is a highly heritable measure of subclinical atherosclerosis and a predictor of cardiovascular diseases. However, knowledge about its shared genetic basis remains limited. The majority of genome-wide association studies have been conducted in individuals of European ancestry, leaving the genetic determinants of cIMT in non-European ancestry populations largely understudied. METHODS:A single-trait genome-wide association study was performed in 22 370 participants from the China Kadoorie Biobank to identify new genetic variants associated with cIMT. We then leveraged cIMT and cardiometabolic disease and trait data from populations of European and East Asian ancestries, to conduct linkage disequilibrium score regression and genome-wide cross-trait analysis, followed by gene-based analysis and Mendelian randomization. RESULTS:We identified 2 genome-wide significant loci for cIMT in the overall China Kadoorie Biobank analysis, including the known APOE locus and a novel locus at GGT5. In addition, a female-specific analysis identified a further novel locus at LINC02732. cIMT showed significant positive genetic correlations with coronary artery disease, type 2 diabetes, body mass index, and systolic blood pressure in both European and East Asian populations. Pleiotropic analysis found 110 and 699 significant pleiotropic variants in 4 trait pairs for East Asian and European populations, respectively, with 27 and 186 colocalized loci detected. Gene-based analysis highlighted important biological pathways involving lipid metabolism and carbohydrate metabolism. Mendelian randomization estimates indicated that higher systolic blood pressure and body mass index, and coronary artery disease and type 2 diabetes, were causal for cIMT, and a reverse effect was observed between cIMT and systolic blood pressure. CONCLUSIONS:Our large-scale genome-wide association study of cIMT identified novel loci in the Chinese population and shared genetic underpinnings and causal relationships with cardiometabolic diseases and traits. These findings potentially provide targets for intervention that may allow the development of new strategies targeting this aspect of atherosclerosis.

Introduction Previous studies suggest that the additional benefits of adhering to a healthy lifestyle may not be considerable for older adults. This study aimed to examine the associations of various lifestyle factors and an integrated healthy lifestyle score with survival and health status in old age. Methods A total of 36,403 participants from the China Kadoorie Biobank were included, with a mean age of 71 years at baseline. Three survival and health statuses were defined: death before age 80, and living beyond age 80 either with or without major chronic diseases (MCDs) including ischemic heart disease, cerebrovascular disease, cancer, and chronic obstructive pulmonary disease. Multinomial logistic regression models were used to examine the associations of smoking, alcohol consumption, dietary habits, total physical activity, body mass index (BMI), waist circumference (WC), body shape, and healthy lifestyle score with survival and health status. The association of BMI with survival and health status was further analyzed through stratified analyses by WC. Results During a median follow-up of 11.5 years, 13,496 participants died and 22,665 developed at least one MCD. Participants who smoked, quit drinking alcohol, had unhealthy dietary habits, and had low levels of physical activity were more likely to die before 80 than their reference group, after controlling for potential confounders. For participants with WC (men/women) <85/80 cm, the ORs (95% CIs) per 5 kg/m2 increment in BMI were 0.68 (0.62, 0.74) for death before age 80 and 1.09 (1.01, 1.17) for living past 80 with MCDs compared to living past 80 without MCDs. In contrast, for those with WC ≥85/80 cm, the corresponding ORs were 1.11 (1.02, 1.21) and 1.16 (1.09, 1.24), respectively. The ORs per 1 additional healthy lifestyle score were 1.16 (1.13, 1.19) for those over 80 with MCDs and 1.25 (1.22, 1.29) for those over 80 without MCDs compared to those dying before 80. Conclusions Adults approximately 70 years old who maintain favorable lifestyle habits may be more likely to have a better health status in later life.

Biological aging is a key determinant of liver disease and mortality, but there is little evidence on noninvasive index for assessment of liver biological aging. We developed the Liver Aging Index (LAI) in the China Kadoorie Biobank (CKB, N = 21,629) using Cox-Gompertz proportional hazards model. The LAI incorporated three clinical factors (body mass index, systolic and diastolic blood pressure), eight plasma biomarkers (glucose, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase), and two imaging biomarkers (fat attenuation parameter and liver stiffness measurement). External validation was conducted in the National Health and Nutrition Examination Survey (NHANES; N = 3412) and the VCTE-Prognosis cohort (N = 12,170, 16 global centers). Across all cohorts, the LAI demonstrated strong discrimination for all-cause mortality (AUROC: 0.764 in NHANES; 0.759 in VCTE-Prognosis), outperforming chronological age (p < 0.05). Liver aging acceleration (LAA), defined as the difference between LAI and chronological age, was associated with substantially elevated risks: each 1-SD increase in LAA conferred a 22%-85% higher risk of all-cause mortality and a 34%-170% higher risk of liver-related event or mortality. Using genetic instruments identified in CKB, we found genetic predisposition to accelerated liver aging was associated with higher risks of cirrhosis and liver cancer (HR = 3.94 [3.20-4.86] and 7.82 [2.05-29.80]), further validated in Biobank Japan. Integrating genetics and proteomics revealed novel pathophysiological involvement of amyloid-beta clearance pathway and amyloid precursor protein in liver aging. These findings demonstrate the feasibility of a noninvasive, liver-specific biological aging index and provide new insights into mechanisms underlying liver aging.