Association of oral health with all-cause and cause-specific mortality in older Chinese adults: A 14-year follow-up of the Guangzhou Biobank Cohort study.

Background: Poor oral hygiene is associated with overall wellness, but evidence regarding associations of oral health with all-cause mortality remain inconclusive. We aimed to examine the associations of oral health with all-cause and cause-specific mortality in middle-aged and older Chinese adults. Methods: 28 006 participants were recruited from 2003-2008 and followed up until 2021. Oral health was assessed by face-to-face interview and causes of death was identified via record linkage. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of multiple potential confounders. Results: During an average of 14.3 years of follow-up, we found that a lower frequency of toothbrushing was associated with higher risks of all-cause mortality with a dose-response pattern (P for trend <0.001). Specially, the adjusted HR (95% CI) (vs. ≥ twice/d) was 1.16 (1.10, 1.22) (P < 0.001) for brushing once/d and 1.27 (1.00, 1.61) (P = 0.048) for < once/d. Similar associations were also found for cardiovascular disease (CVD), stroke, and respiratory disease mortality, but not for ischemic heart disease (IHD) and cancer mortality. A greater number of missing teeth was also associated with higher risks of all-cause, CVD, stroke, and respiratory disease mortality with a dose-response pattern (all P for trend <0.05). The association of missing teeth with all-cause mortality was stronger in lower-educated participants. Conclusions: Both less frequent toothbrushing and a greater number of missing teeth were associated with higher risks of all-cause, CVD, stroke, and respiratory disease mortality, showing dose-response patterns, but not with IHD and cancer mortality. Moreover, the dose-response association of missing teeth with all-cause mortality was stronger in lower-educated participants.

Do iron homeostasis biomarkers mediate the associations of liability to type 2 diabetes and glycemic traits in liver steatosis and cirrhosis: a two-step Mendelian randomization study.

BACKGROUND: Previous studies, including Mendelian randomization (MR), have demonstrated type 2 diabetes (T2D) and glycemic traits are associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, few studies have explored the underlying pathway, such as the role of iron homeostasis. METHODS: We used a two-step MR approach to investigate the associations of genetic liability to T2D, glycemic traits, iron biomarkers, and liver diseases. We analyzed summary statistics from various genome-wide association studies of T2D (n = 933,970), glycemic traits (n ≤ 209,605), iron biomarkers (n ≤ 246,139), MASLD (n ≤ 972,707), and related biomarkers (alanine aminotransferase (ALT) and proton density fat fraction (PDFF)). Our primary analysis was based on inverse-variance weighting, followed by several sensitivity analyses. We also conducted mediation analyses and explored the role of liver iron in post hoc analysis. RESULTS: Genetic liability to T2D and elevated fasting insulin (FI) likely increased risk of liver steatosis (ORliability to T2D: 1.14 per doubling in the prevalence, 95% CI: 1.10, 1.19; ORFI: 3.31 per log pmol/l, 95% CI: 1.92, 5.72) and related biomarkers. Liability to T2D also likely increased the risk of developing liver cirrhosis. Genetically elevated ferritin, serum iron, and liver iron were associated with higher risk of liver steatosis (ORferritin: 1.25 per SD, 95% CI 1.07, 1.46; ORliver iron: 1.15 per SD, 95% CI: 1.05, 1.26) and liver cirrhosis (ORserum iron: 1.31, 95% CI: 1.06, 1.63; ORliver iron: 1.34, 95% CI: 1.07, 1.68). Ferritin partially mediated the association between FI and liver steatosis (proportion mediated: 7%, 95% CI: 2-12%). CONCLUSIONS: Our study provides credible evidence on the causal role of T2D and elevated insulin in liver steatosis and cirrhosis risk and indicates ferritin may play a mediating role in this association.

Association of childhood food consumption and dietary pattern with cardiometabolic risk factors and metabolomics in late adolescence: prospective evidence from 'Children of 1997' birth cohort.

BACKGROUND: Healthy diet might protect against cardiometabolic diseases, but uncertainty exists about its definition and role in adolescence. METHOD: In a subset of Hong Kong's 'Children of 1997' birth cohort (n=2844 out of 8327), we prospectively examined sex-specific associations of food consumption and dietary pattern, proxied by the Global Diet Quality Score (GDQS) at~12.0 years, with cardiometabolic risk factors and metabolomics at~17.6 years. RESULT: Higher vegetable (-0.04 SD, 95% CIs: -0.09 to 0.00) and soy consumption (-0.05 SD, 95% CI: -0.09 to -0.01) were associated with lower waist-to-hip ratio. Higher fruit and vegetable consumption were associated with lower fasting glucose (p<0.05). Higher fish consumption was associated with 0.06 SD (95% CI: 0.01 to 0.10) high-density lipoprotein cholesterol and -0.07 SD (95% CI: -0.11 to -0.02) triglycerides. After correcting for multiple comparisons (p<0.001), higher fish, fruit and vegetable consumption were associated with higher fatty acid unsaturation, higher concentration and percentage of omega-3 and a lower ratio of omega-6/omega-3. At nominal significance (p<0.05), higher fish consumption was associated with lower very-low-density lipoprotein and triglycerides relevant metabolomics. Higher vegetable and fruit consumption were associated with lower glycolysis-related metabolomics. Lower sugar-sweetened beverages (SSBs) consumption was associated with lower branched-chain amino acids. Similar associations with adiposity and metabolomics biomarkers were observed for GDQS. CONCLUSIONS: Higher consumption of fruit, vegetables and fish and lower ice cream and SSBs consumption were associated with lower cardiometabolic risk in adolescents.

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.

A two-sample Mendelian randomization study explores metabolic profiling of different glycemic traits.

We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.

Incidence of Dementia and Alzheimer's Disease, Genetic Susceptibility, and Grip Strength Among Older Adults.

BACKGROUND: Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown. METHODS: This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers. RESULTS: The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15-2.59) and 3.00 (95% CI: 2.61-3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64-0.74) for incident dementia, and 0.74 (95% CI: 0.66-0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314). CONCLUSIONS: Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD.

Adherence to a healthy lifestyle, genetic susceptibility to abdominal obesity, cardiometabolic risk markers, and risk of coronary heart disease.

BACKGROUND: Little is known about whether the association between genetic susceptibility to high waist-to-hip ratio (WHR), a measure of abdominal obesity, and incident coronary heart disease (CHD) is modified by adherence to a healthy lifestyle. OBJECTIVES: To explore the interplay of genetic susceptibility to high WHR and adherence to a healthy lifestyle on incident CHD. METHODS: This study included 282,316 white British individuals from the UK Biobank study. Genetic risk for high WHR was estimated in the form of weighted polygenic risk scores (PRSs), calculated based on 156 single-nucleotide polymorphisms. Lifestyle scores were calculated based on 5 healthy lifestyle factors: regular physical activity, no current smoking, a healthy diet, <3 times/wk of alcohol consumption and 7-9 h/d of sleep. Incident CHD (n = 11,635) was accrued over a median 13.8 y of follow-up, and 12 individual cardiovascular disease risk markers assessed at baseline. RESULTS: Adhering to a favorable lifestyle (4-5 healthy factors) was associated with a 25% (hazard ratio: 0.75, 95% confidence interval: 0.70, 0.81) lower hazard of CHD compared with an unfavorable lifestyle (0-1 factor), independent of PRS for high WHR. Estimated 12-y absolute risk of CHD was lower for a favorable lifestyle at high genetic risk (1.73%) and medium genetic risk (1.67%) than for an unfavorable lifestyle at low genetic risk (2.08%). Adhering to a favorable lifestyle was associated with healthier levels of cardiovascular disease risk markers (except random glucose and high-density lipoprotein), independent of PRS for high WHR. CONCLUSIONS: Individuals who have high or medium genetic risk of abdominal obesity but adhere to a healthy lifestyle may have a lower risk of developing CHD, compared with those who have low genetic risk and an unhealthy lifestyle. Future clinical trials of lifestyle modification could be implemented for individuals at high genetic risk of abdominal obesity for the primary prevention of CHD events.

Assessing the safety of lipid-modifying medications among Chinese adolescents: a drug-target Mendelian randomization study.

BACKGROUND: With increasing hypercholesterolemia prevalence in East Asian adolescents, pharmacologic interventions (e.g., HMGCR inhibitors (statins) and PCSK9 inhibitors) may have to be considered although their longer-term safety in the general adolescent population is unclear. This study aims to investigate the longer-term safety of HMGCR inhibitors and PCSK9 inhibitors among East Asian adolescents using genetics. METHODS: A drug-target Mendelian randomization study leveraging the Global Lipid Genetics Consortium (East Asian, n = 146,492) and individual-level data from Chinese participants in the Biobank clinical follow-up of Hong Kong's "Children of 1997" birth cohort (n = 3443, aged ~ 17.6 years). Safety outcomes (n = 100) included anthropometric and hematological traits, renal, liver, lung function, and other nuclear magnetic resonance metabolomics. Positive control outcomes were cholesterol markers from the "Children of 1997" birth cohort and coronary artery disease from Biobank Japan. RESULTS: Genetic inhibition of HMGCR and PCSK9 were associated with reduction in cholesterol-related NMR metabolomics, e.g., apolipoprotein B (HMGCR: beta [95% CI], - 1.06 [- 1.52 to - 0.60]; PCSK9: - 0.93 [- 1.56 to - 0.31]) and had the expected effect on the positive control outcomes. After correcting for multiple comparisons (p-value < 0.006), genetic inhibition of HMGCR was associated with lower linoleic acid - 0.79 [- 1.25 to - 0.35]. Genetic inhibition of PCSK9 was not associated with the safety outcomes assessed. CONCLUSIONS: Statins and PCSK9 inhibitors in East Asian adolescents appeared to be safe based on the outcomes concerned. Larger studies were warranted to verify these findings. This study serves as a proof of principle study to inform the medication safety among adolescents via genetics.

Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study.

BACKGROUND: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). METHODS: Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. FINDINGS: Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46-0.84), lower levels of body mass index (BMI) (ß = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (ß = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (ß = -0.29, 95% CI = -0.39 to -0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. INTERPRETATION: This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. FUNDING: Funding information is provided in the Acknowledgements.

Mode of transport, genetic susceptibility, and incidence of coronary heart disease.

BACKGROUND: Car use has been associated with higher risk of coronary heart disease (CHD). However, whether the associations of transport modes with CHD vary by genetic susceptibility to CHD are unknown. This study aims to investigate the associations of genetic susceptibility and modes of transport with incidence of CHD. METHODS: We included 339,588 white British participants from UK Biobank with no history of CHD or stroke at baseline or within two years of follow-up (52.3% in work). Genetic susceptibility to CHD was quantified through weighted polygenic risk scores derived from 300 single-nucleotide polymorphisms related to CHD risk. Categories of transport mode included exclusive car use and alternatives to the car (e.g., walking, cycling and public transport), separately for non-commuting (e.g., getting about [n=339,588] excluding commuting for work), commuting (in the sub-set in work [n=177,370] who responded to the commuting question), and overall transport (transport mode for both commuting and non-commuting [n=177,370]). We used Cox regression with age as the underlying timescale to estimate hazard ratios (HR) of CHD (n=13,730; median 13.8-year follow-up) and tested the interaction between genetic susceptibility and travel modes with adjustment for confounders. RESULTS: Compared to those using alternatives to the car, hazards of CHD were higher for exclusive use of cars for overall transport (HR: 1.16, 95% confidence interval (CI): 1.08-1.25), non-commuting (HR: 1.08, 95% CI: 1.04-1.12) and commuting (HR: 1.16, 95% CI: 1.09-1.23), after adjusting for confounders plus genetic susceptibility. HRs of CHD were 1.45 (95% CI: 1.38-1.52) and 2.04 (95% CI: 1.95-2.12) for the second and third tertile of genetic susceptibility to CHD, respectively, compared to the first. There was, in general, no strong evidence of interactions between genetic susceptibility and categories of overall, non-commuting and commuting transport. Estimated 10-year absolute risk of CHD was lower for the alternatives to the car across strata of genetic susceptibility, compared with exclusive use of cars for overall, non-commuting and commuting transport. CONCLUSION: Exclusive use of cars was associated with a relatively higher risk of CHD across all strata of genetic susceptibility. Using alternatives to the car should be encouraged for prevention of CHD for the general population including individuals at high genetic risk.

Association of iron homeostasis biomarkers in type 2 diabetes and glycaemic traits: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Mendelian randomization (MR) studies show iron positively associated with type 2 diabetes (T2D) but included potentially biasing hereditary haemochromatosis variants and did not assess reverse causality. METHODS: We assessed the relation of iron homeostasis with T2D and glycaemic traits bidirectionally, using genome-wide association studies (GWAS) of iron homeostasis biomarkers [ferritin, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT) (n ≤ 246 139)], T2D (DIAMANTE n = 933 970 and FinnGen n = 300 483), and glycaemic traits [fasting glucose (FG), 2-h glucose, glycated haemoglobin (HbA1c) and fasting insulin (FI) (n ≤ 209 605)]. Inverse variance weighting (IVW) was the main analysis, supplemented with sensitivity analyses and assessment of mediation by hepcidin. RESULTS: Iron homeostasis biomarkers were largely unrelated to T2D, although serum iron was potentially associated with higher T2D [odds ratio: 1.07 per standard deviation; 95% confidence interval (CI): 0.99 to 1.16; P-value: 0.078) in DIAMANTE only. Higher ferritin, serum iron, TSAT and lower TIBC likely decreased HbA1c, but were not associated with other glycaemic traits. Liability to T2D likely increased TIBC (0.03 per log odds; 95% CI: 0.01 to 0.05; P-value: 0.005), FI likely increased ferritin (0.29 per log pmol/L; 95% CI: 0.12 to 0.47; P-value: 8.72 x 10-4). FG likely increased serum iron (0.06 per mmol/L; 95% CI: 0.001 to 0.12; P-value: 0.046). Hepcidin did not mediate these associations. CONCLUSION: It is unlikely that ferritin, TSAT and TIBC cause T2D although an association for serum iron could not be excluded. Glycaemic traits and liability to T2D may affect iron homeostasis, but mediation by hepcidin is unlikely. Corresponding mechanistic studies are warranted.

Breastfeeding and ApoB in late adolescence: a Hong Kong birth cohort study.

Breastfeeding is widely promoted. Experimental evidence concerning long-term benefits is limited. Observational studies are open to bias from confounding by socio-economic position. We assessed the association of breastfeeding with late adolescent lipid sub-fractions, particularly apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-c), overall and by sex. We took advantage of a setting where breastfeeding has little association with higher socio-economic position and where several results from randomized controlled trials of breastfeeding promotion have been replicated. We used the population-representative "Children of 1997" birth cohort comprising 88% of births in Hong Kong in April and May 1997. Associations of breastfeeding in the first 3 months of life (never, mixed, exclusive) with lipid sub-fractions were obtained using linear regression adjusted for potential confounders including parental socio-economic position, maternal place of birth, type of delivery, gestational age, and birth weight. Differences by sex were assessed. Multiple imputation and inverse probability weighting were used to recover the original sample. Of the 3462 participants included, mean age was 17.6 years and 48.8% were girls. Mean ApoB was 0.74 g/L (standard deviation 0.15). Exclusive versus never breastfeeding was associated with lower ApoB (-0.027 g/L, 95% confidence interval (CI)-0.046 to-0.007, p = 0.007) and lower non-HDL-c (-0.143 mmol/L, 95% CI-0.237 to-0.048) with similar estimates by sex. CONCLUSION: Breastfeeding may provide some population-level lifelong protection against cardiovascular disease. This study supports policies promoting breastfeeding as a modifiable exposure that contributes to a healthy start in life as an investment for lifelong cardiovascular disease prevention. WHAT IS KNOWN: • Apolipoprotein B (ApoB) is a recognized risk factor for cardiovascular disease, but whether breastfeeding affects ApoB in later life overall and by sex is unknown. WHAT IS NEW: • Exclusive breastfeeding in the first 3 months of life was associated with lower ApoB in late adolescence, with similar estimates for both sexes. • The inverse association of breastfeeding with ApoB suggests that breastfeeding could reduce cardiovascular disease and overall mortality over the lifespan.

Environment- and epigenome-wide association study of obesity in 'Children of 1997' birth cohort.

Background: Increasing childhood obesity is a global issue requiring potentially local solutions to ensure it does not continue into adulthood. We systematically identified potentially modifiable targets of obesity at the onset and end of puberty in Hong Kong, the most economically developed major Chinese city. Methods: We conducted an environment-wide association study (EWAS) and an epigenome-wide association study of obesity to systematically assess associations with body mass index (BMI) and waist-hip ratio (WHR) in Hong Kong's population-representative 'Children of 1997' birth cohort. Univariable linear regression was used to select exposures related to obesity at ~11.5 years (BMI and obesity risk n ≤ 7119, WHR n = 5691) and ~17.6 years (n = 3618) at Bonferroni-corrected significance, and multivariable regression to adjust for potential confounders followed by replicated multivariable regression (n = 308) and CpG by CpG analysis (n = 286) at ~23 years. Findings were compared with evidence from published randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. Results: At ~11.5 and~17.6 years the EWAS identified 14 and 37 exposures associated with BMI, as well as 7 and 12 associated with WHR, respectively. Most exposures had directionally consistent associations at ~23 years. Maternal second-hand smoking, maternal weight, and birth weight were consistently associated with obesity. Diet (including dairy intake and artificially sweetened beverages), physical activity, snoring, binge eating, and earlier puberty were positively associated with BMI at ~17.6 years, while eating before sleep was inversely associated with BMI at ~17.6 years. Findings for birth weight, dairy intake, and binge eating are consistent with available evidence from RCTs or MR studies. We found 17 CpGs related to BMI and 17 to WHR. Conclusions: These novel insights into potentially modifiable factors associated with obesity at the outset and the end of puberty could, if causal, inform future interventions to improve population health in Hong Kong and similar Chinese settings. Funding: This study including the follow-up survey and epigenetics testing was supported by the Health and Medical Research Fund Research Fellowship, Food and Health Bureau, Hong Kong SAR Government (#04180097). The DNA extraction of the samples used for epigenetic testing was supported by CFS-HKU1.

The influence of growth and sex hormones on risk of alzheimer's disease: a mendelian randomization study.

Alzheimer's disease is more prevalent in women, possibly due to sex or growth hormones but existing evidence is inconclusive. We investigated whether genetically predicted sex and growth hormones are associated with risk of Alzheimer's disease. Genetic variants strongly and independently predicting insulin-like growth factor 1 (IGF-1), testosterone and sex hormone-binding globulin (SHBG) were obtained from large, published genome wide associations studies (GWAS) and applied to GWAS of Alzheimer's disease based on clinical diagnosis (cases = 21,982, control = 41,944) from the International Genomics of Alzheimer's Project and the UK Biobank parental (maternal cases = 27,696; paternal cases = 14,338) and siblings' diagnosis (cases = 2,171) as proxy cases. Published GWAS summary statistics were used in our analyses. Estimates were obtained from inverse variance weighting with sensitivity analysis (i.e., MR-Egger, weighted median and MR-PRESSO). Multivariable analyses adjusted for pleiotropic effects and possible sources of selection bias were also performed. Genetically predicted higher total testosterone may reduce the risk of paternal Alzheimer's disease (odds ratio (OR) 0.86, 95% confidence interval (CI) 0.76 to 0.97, per SD increase in testosterone) and in meta-analysis for women (OR 0.92, 95% CI 0.87, 0.98) with directionally similar results from other analyses. SHBG were not associated with Alzheimer's disease. IGF-1 in women was inversely associated with risk of clinical Alzheimer's disease in sensitivity analysis but not in the main analysis. These results suggest genetically predicted higher total testosterone may lower risk of Alzheimer's disease. The role of testosterone and the immune system in Alzheimer's disease could be further investigated.

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.