Dataset Information

Cohort Differences in the Associations of Selected Candidate Genes With Risk of All-Cause Mortality at Advanced Ages.

ABSTRACT: Considerable efforts have been made to identify the genetic basis of human longevity, with only limited progress. One important drawback of current genetic studies is the limited knowledge of gene-environment interaction. Using 2 cohorts of long-lived individuals born in 1905 and 1915 in Denmark, we performed survival analysis to estimate risk of mortality for major candidate genes of aging and longevity and their cohort effects. Through statistical modeling that combines individual genetic and survival information with cohort-specific survival data, we estimated the relative risks of mortality from ages 95 to 103 years associated with genetic variants in apolipoprotein E (APOE), forkhead box class O3a, clusterin, and phosphatidylinositol binding clathrin assembly protein. Our analysis estimated a decreased risk of carrying the APOE$\varepsilon $4 allele (change in risk = -0.403, 95% confidence interval (CI): -0.831, 0.021; P = 0.040) in men of the later cohort, although the allele itself was harmful to survival across sexes (relative risk = 1.161, 95% CI: 1.027, 1.345; P = 0.026). We also estimated a cohort effect of increased risk for the minor allele of rs3851179 in phosphatidylinositol binding clathrin assembly protein with borderline significance (change in risk = 0.165, 95% CI: -0.010, 0.331; P = 0.052) in women. Our estimated significant cohort effect on APOE$\varepsilon $4 is indicative of the interplay between the gene and the changing environment that modulates survival at extreme ages.

SUBMITTER: Tan Q

PROVIDER: S-EPMC7393313 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundInconsistent results have been reported in developed countries for relationships between sedentary behavior and cancer incidence and mortality, and evidence from the Chinese population is scarce. This study aimed to investigate such relationships in large Chinese population-based prospective cohorts and to explore the joint effect and interaction of sedentary behavior and moderate-to-vigorous physical activity (MVPA) on these relationships.MethodsWe included 95,319 Chinese adults without cancer from 3 large cohorts and assessed their sedentary behavior and physical activity with a unified questionnaire. Cancer incidence and mortality were confirmed by interviewing participants or their proxies and checking hospital records and death certificates. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for cancer and mortality were estimated using Cox proportional hazards regression models.ResultsDuring 559,002 person-years of follow-up, 2388 cancer events, 1571 cancer deaths, and 4562 all-cause deaths were recorded. Sedentary behavior was associated with increased risk of developing cancer and deaths in a dose-response manner. The multivariable-adjusted HRs (95%CIs) were the following: HR = 1.16, 95%CI: 1.01‒1.33; HR = 1.24, 95%CI: 1.04‒1.48; and HR = 1.15, 95%CI: 1.04‒1.28 for cancer incidence, cancer mortality, and all-cause mortality, respectively, for those having ≥10 h/day of sedentary time compared with those having <6 h/day of sedentary time. Sedentary populations (≥10 h/day) developed cancer or died 4.09 years and 2.79 years earlier, respectively, at the index age of 50 years. Failure to achieve the recommended level of MVPA may further aggravate the adverse associations, with the highest cancer and mortality risks being observed among participants with both ≥10 h/day of sedentary time and <150 min/week of MVPA. Limitations of this study include the fact that physical activity information was obtained via questionnaire instead of objective measurement and that there were insufficient incident cases for the analysis of associations between sedentary behavior and site-specific cancers.ConclusionSedentary behavior was associated with an increased risk of cancer and all-cause mortality among Chinese adults, especially for those with ≥10 h/day of sedentary time. It is necessary to reduce sedentary time, in addition to increasing MVPA levels, for the prevention of cancer and premature death.

Project description:BackgroundIncome volatility is on the rise and presents a growing public health problem. Because in many epidemiological studies income is measured at a single point in time, the association of long-term income volatility with incident cardiovascular disease (CVD) and mortality has not been adequately explored. The goal of this study was to examine associations of income volatility from 1990 to 2005 with incident CVD and all-cause mortality in the subsequent 10 years.MethodsThe Coronary Artery Risk Development in Young Adults Study is an ongoing prospective cohort study conducted within urban field centers in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. We studied 3937 black and white participants 23 to 35 years of age in 1990 (our study baseline). Income volatility was defined as the intraindividual SD of the percent change in income across 5 assessments from 1990 to 2005. An income drop was defined as a decrease of ≥25% from the previous visit and less than the participant's average income from 1990 to 2005. CVD events (fatal and nonfatal) and all-cause mortality between 2005 and 2015 were adjudicated with the use of medical records and death certificates. CVD included primarily acute events related to heart disease and stroke.ResultsA total of 106 CVD events and 164 deaths occurred between 2005 and 2015 (incident rate, 2.76 and 3.66 per 1000 person-years, respectively). From Cox models adjusted for sociodemographic, behavioral, and CVD risk factors, higher income volatility and more income drops were associated with greater CVD risk (high versus low volatility: hazard ratio, 2.07; 95% CI, 1.10-3.90; ≥2 versus 0 income drops: hazard ratio, 2.54; 95% CI, 1.24-5.19) and all-cause mortality (high versus low volatility: hazard ratio, 1.78; 95% CI,1.03-3.09; ≥2 versus 0 income drops: hazard ratio, 1.92; 95% CI, 1.07-3.44).ConclusionsIn a cohort of relatively young adults, income volatility and drops during a 15-year period of formative earning years were independently associated with a nearly 2-fold risk of CVD and all-cause mortality.

Project description:The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time.Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II). DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (MAOA), lipoprotein lipase (LPL), paraoxonase 1 and 2 (PON1 and PON2), leptin receptor (LEPR), tumor necrosis factor-alpha (TNFalpha), and peroxisome proliferative activated receptor-gamma and -delta (PPARG and PPARD). Data on height and weight in 1989 (CLUE II baseline) and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR) estimates and 95% confidence intervals (CI) for each SNP and mortality outcomes.The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p < 0.05) were observed between PPARG rs4684847 and all-cause mortality (CC: reference; CT: RR 0.99, 95% CI 0.89, 1.11; TT: RR 0.60, 95% CI 0.39, 0.93) and cancer-related mortality (CC: reference; CT: RR 1.01, 95% CI 0.82, 1.25; TT: RR 0.22, 95% CI 0.06, 0.90) and TNFalpha rs1799964 and cancer-related mortality (TT: reference; CT: RR 1.23, 95% CI 1.03, 1.47; CC: RR 0.83, 95% CI 0.54, 1.28). Additional analyses showed significant associations between SNPs in LEPR with BMI (rs1137101) and change in BMI over time (rs1045895 and rs1137101).Findings from this cohort study suggest that the selected SNPs are not associated with overall or cause-specific death, although several LEPR SNPs may be related to BMI and BMI change over time.

Project description:Objective To evaluate the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality.Design Longitudinal study with up to 32 years of follow-up.Setting Nurses' Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012).Participants 74?582 women from the Nurses' Health Study and 39?284 men from the Health Professionals Follow-up Study who were free from cardiovascular disease and cancer at baseline.Main outcome measures Exposures included body mass index (BMI), score on the alternate healthy eating index, level of physical activity, smoking habits, and alcohol drinking while outcome was mortality (all cause, cardiovascular, cancer). Cox proportional hazard models were used to calculate the adjusted hazard ratios of all cause, cancer, and cardiovascular mortality with their 95% confidence intervals across categories of BMI, with 22.5-24.9 as the reference.Results During up to 32 years of follow-up, there were 30?013 deaths (including 10?808 from cancer and 7189 from cardiovascular disease). In each of the four categories of BMI studied (18.5-22.4, 22.5-24.9, 25-29.9, ?30), people with one or more healthy lifestyle factors had a significantly lower risk of total, cardiovascular, and cancer mortality than individuals with no low risk lifestyle factors. A combination of at least three low risk lifestyle factors and BMI between 18.5-22.4 was associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37, 0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none of the four low risk lifestyle factors.Conclusion Although people with a higher BMI can have lower risk of premature mortality if they also have at least one low risk lifestyle factor, the lowest risk of premature mortality is in people in the 18.5-22.4 BMI range with high score on the alternate healthy eating index, high level of physical activity, moderate alcohol drinking, and who do not smoke. It is important to consider diet and lifestyle factors in the evaluation of the association between BMI and mortality.

Dataset Information

Cohort Differences in the Associations of Selected Candidate Genes With Risk of All-Cause Mortality at Advanced Ages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets