Genetic risk factors have a substantial impact on healthy life years.
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ABSTRACT:
SUBMITTER: Jukarainen S
PROVIDER: S-EPMC9499866 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Genetic risk factors have a substantial impact on healthy life years.
Jukarainen Sakari S Kiiskinen Tuomo T Kuitunen Sara S Havulinna Aki S AS Karjalainen Juha J Cordioli Mattia M Rämö Joel T JT Mars Nina N Samocha Kaitlin E KE Ollila Hanna M HM Pirinen Matti M Ganna Andrea A
Nature medicine 20220912 9
The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying ...[more]
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Project description:BackgroundAmericans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population.MethodsUsing data from the Nurses' Health Study (1980-2014; n=78 865) and the Health Professionals Follow-up Study (1986-2014, n=44 354), we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m2, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%), and estimated hazard ratios for the association of total lifestyle score (0-5 scale) with mortality. We used data from the NHANES (National Health and Nutrition Examination Surveys; 2013-2014) to estimate the distribution of the lifestyle score and the US Centers for Disease Control and Prevention WONDER database to derive the age-specific death rates of Americans. We applied the life table method to estimate life expectancy by levels of the lifestyle score.ResultsDuring up to 34 years of follow-up, we documented 42 167 deaths. The multivariable-adjusted hazard ratios for mortality in adults with 5 compared with zero low-risk factors were 0.26 (95% confidence interval [CI], 0.22-0.31) for all-cause mortality, 0.35 (95% CI, 0.27-0.45) for cancer mortality, and 0.18 (95% CI, 0.12-0.26) for cardiovascular disease mortality. The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6-66.7) for all-cause mortality, 51.7% (95% CI, 37.1-62.9) for cancer mortality, and 71.7% (95% CI, 58.1-81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3-29.8) for women and 25.5 years (95% CI, 24.7-26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3-44.9) for women and 37.6 years (95% CI, 35.8-39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8-16.2) longer among female Americans with 5 low-risk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1-14.2).ConclusionsAdopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults.
| S-EPMC6207481 | biostudies-literature
Project description:Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10-30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.
| S-EPMC4836858 | biostudies-literature
Project description:BackgroundThe European Union has used Healthy Life Years (HLY) as an indicator to monitor the health of its aging populations. Scholarly and popular interest in HLY across countries has grown, particularly regarding the ranking of countries. It is important to note that HLY is based on self-assessments of activity limitations, raising the possibility that it might be influenced by differences in health reporting behaviours between populations, a phenomenon known as differential item functioning (DIF).MethodsWe estimated DIF-adjusted HLY at age 50 for Belgium, France, Germany, Greece, Italy, the Netherlands, Spain, and Sweden to determine the extent to which differences in HLY might be influenced by reporting heterogeneity across countries. We used anchoring vignettes, taken from the 2004 Survey of Health, Ageing and Retirement in Europe, to estimate DIF-adjusted prevalence rates of activity limitations measured by the Global Activity Limitations Indicator (GALI). The Sullivan method was used to calculate DIF-adjusted HLY.ResultsChanges in HLY before and after adjustment ranged from a 1.20-year decrease for men in Italy to a 1.61-year increase for women in Spain. Adjustment for DIF produced changes in the rankings of the countries by HLY, with upward and downward movements of up to three positions.ConclusionOur results show that DIF is likely to affect HLY estimates, thereby posing a challenge to the validity of comparisons of HLY across European countries. The findings suggest that HLY should be used to monitor population health status within a country, rather than to make comparisons across countries.
| S-EPMC10710331 | biostudies-literature
Project description:BACKGROUND:Heavy menstrual bleeding (HMB) has been shown to have a profound negative impact on women's quality of life and lead to increases in health care costs; however, data on HMB among Chinese population is still rather limited. The present study therefore aimed to determine the current prevalence and risk factors of subjectively experienced HMB in a community sample of Chinese reproductive-age women, and to evaluate its effect on daily life. METHODS:We conducted a questionnaire survey in 2356 women aged 18-50 years living in Beijing, China, from October 2014-July 2015. A multivariate logistic regression model was used to identify risk factors for HMB. RESULTS:Overall, 429 women experienced HMB, giving a prevalence of 18.2%. Risk factors associated with HMB included uterine fibroids (adjusted odds ratio [OR] =2.12, 95% confidence interval [CI] = 1.42-3.16, P < 0.001) and multiple abortions (≥3) (adjusted OR = 3.44, 95% CI = 1.82-6.49, P < 0.001). Moreover, women in the younger age groups (≤24 and 25-29 years) showed higher risks for HMB, and those who drink regularly were more likely to report heavy periods compared with never drinkers (adjusted OR = 2.78, 95% CI = 1.20-6.46, P = 0.017). In general, women experiencing HMB felt more practical discomforts and limited life activities while only 81 (18.9%) of them had sought health care for their heavy bleeding. CONCLUSIONS:HMB was highly prevalent among Chinese women and those reporting heavy periods suffered from greater menstrual interference with daily lives. More information and health education programs are urgently needed to raise awareness of the consequences of HMB, encourage women to seek medical assistance and thus improve their quality of life.
| S-EPMC6360654 | biostudies-literature
Project description:Background & aimsThe combined effects of healthy lifestyle factors on colorectal cancer (CRC) risk are unclear. We aimed to develop a healthy lifestyle score, to investigate the joint effects of modifiable lifestyle factors on reduction of CRC risk and determine whether associations differ with genetic risk.MethodsWe collected data from a large population-based case-control study in Germany and used multiple logistic regression analyses to examine associations between the healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness) and CRC risk. We created a genetic risk score, based on 53 risk variants, to investigate the association of the healthy lifestyle score and risk of CRC, stratified by genetic risk.ResultsWe included 4092 patients with CRC and 3032 individuals without CRC (controls) in our analysis. In adjusted models, compared with participants with 0 or 1 healthy lifestyle factor, participants with 2 (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.67-1.06), 3 (OR 0.62; 95% CI 0.50-0.77), 4 (OR 0.53; 95% CI 0.42-0.66), or 5 (OR 0.33; 95% CI 0.26-0.43) healthy lifestyle factors had increasingly lower risks of CRC (P trend <.0001). We found no differences among subgroups stratified by genetic risk score, history of colonoscopy, or family history of CRC. Overall, 45% of CRC cases (95% CI 34%-53%) could be attributed to nonadherence to all 5 healthy lifestyle behaviors.ConclusionsIn a large population-based case-control study, we identified a combination of lifestyle factors that appears to reduce risk of CRC, regardless of the patient's genetic profile. These results reinforce the importance of primary prevention of CRC.
| S-EPMC6279591 | biostudies-literature
Project description:Healthy Life Years (HLY) is a prominent summary indicator for evaluating and comparing the levels of population health status across Europe. Variations in HLY, however, do not necessarily reflect underlying differences in health and mortality levels among countries and the indicator is particularly sensitive when broken down by subpopulations. For instance, despite European countries showing large HLY inequalities by educational level, these countries are also heterogenous regarding their population composition by educational attainment, which most likely affects their HLY levels. We demonstrate how this compositional effect shapes HLY levels by providing estimates for HLY by educational attainment and gender for 16 European countries using the Sullivan method. We use prevalence data about limitations in daily activities from the European Union Statistics on Income and Living Conditions (EU-SILC) and mortality data from the Eurostat database. Finally, we adjust for compositional effects by means of standardization. The education-adjusted HLY estimates do not differ much from conventional HLY. Yet, we find that in some countries HLY levels are indeed affected by the population composition by educational attainment. For example, low-, medium-, and high educated individuals in Portugal show more HLY than their counterparts in Poland. Still, Poland's total HLY value slightly exceeds that of Portugal, indicating favorable health and mortality conditions in Poland. It is Poland's lower relative number of low educated individuals in its population that is responsible for producing this higher total HLY value. We conclude that differentials in HLY due to differences in the relative size of educational subpopulations are generally small in HLY across Europe but they can play an important role for countries that experienced large differences in their educational expansion.
| S-EPMC8255240 | biostudies-literature
Project description:Healthy Life Years (HLY) is a prominent summary indicator for evaluating and comparing the levels of population health status across Europe. Variations in HLY, however, do not necessarily reflect underlying differences in health and mortality levels among countries and the indicator is particularly sensitive when broken down by subpopulations. For instance, despite European countries showing large HLY inequalities by educational level, these countries are also heterogenous regarding their population composition by educational attainment, which most likely affects their HLY levels. We demonstrate how this compositional effect shapes HLY levels by providing estimates for HLY by educational attainment and gender for 16 European countries using the Sullivan method. We use prevalence data about limitations in daily activities from the European Union Statistics on Income and Living Conditions (EU-SILC) and mortality data from the Eurostat database. Finally, we adjust for compositional effects by means of standardization. The education-adjusted HLY estimates do not differ much from conventional HLY. Yet, we find that in some countries HLY levels are indeed affected by the population composition by educational attainment. For example, low-, medium-, and high educated individuals in Portugal show more HLY than their counterparts in Poland. Still, Poland's total HLY value slightly exceeds that of Portugal, indicating favorable health and mortality conditions in Poland. It is Poland's lower relative number of low educated individuals in its population that is responsible for producing this higher total HLY value. We conclude that differentials in HLY due to differences in the relative size of educational subpopulations are generally small in HLY across Europe but they can play an important role for countries that experienced large differences in their educational expansion.
| S-EPMC8255240 | biostudies-literature
Project description:Healthy Life Years (HLY) is a prominent summary indicator for evaluating and comparing the levels of population health status across Europe. Variations in HLY, however, do not necessarily reflect underlying differences in health and mortality levels among countries and the indicator is particularly sensitive when broken down by subpopulations. For instance, despite European countries showing large HLY inequalities by educational level, these countries are also heterogenous regarding their population composition by educational attainment, which most likely affects their HLY levels. We demonstrate how this compositional effect shapes HLY levels by providing estimates for HLY by educational attainment and gender for 16 European countries using the Sullivan method. We use prevalence data about limitations in daily activities from the European Union Statistics on Income and Living Conditions (EU-SILC) and mortality data from the Eurostat database. Finally, we adjust for compositional effects by means of standardization. The education-adjusted HLY estimates do not differ much from conventional HLY. Yet, we find that in some countries HLY levels are indeed affected by the population composition by educational attainment. For example, low-, medium-, and high educated individuals in Portugal show more HLY than their counterparts in Poland. Still, Poland's total HLY value slightly exceeds that of Portugal, indicating favorable health and mortality conditions in Poland. It is Poland's lower relative number of low educated individuals in its population that is responsible for producing this higher total HLY value. We conclude that differentials in HLY due to differences in the relative size of educational subpopulations are generally small in HLY across Europe but they can play an important role for countries that experienced large differences in their educational expansion.
| S-EPMC8255240 | biostudies-literature
Project description:BackgroundGenetic and lifestyle factors both contribute to the pathogenesis of bladder cancer, but the extent to which the increased genetic risk can be mitigated by adhering to a healthy lifestyle remains unclear. We aimed to investigate the association of combined lifestyle factors with bladder cancer risk within genetic risk groups.MethodsWe conducted a prospective study of 375 998 unrelated participants of European ancestry with genotype and lifestyle data and free of cancer from the UK biobank. We generated a polygenic risk score (PRS) using 16 single nucleotide polymorphisms and a healthy lifestyle score based on body weight, smoking status, physical activity, and diet. Cox models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of genetic and lifestyle factors on bladder cancer.ResultsDuring a median follow-up of 11.8 years, 880 participants developed bladder cancer. Compared with those with low PRS, participants with intermediate and high PRS had a higher risk of bladder cancer (HR 1.29, 95% CI 1.07-1.56; HR 1.63, 95% CI 1.32-2.02, respectively). An optimal lifestyle was associated with an approximately 50% lower risk of bladder cancer than a poor lifestyle across all genetic strata. Participants with a high genetic risk and a poor lifestyle had 3.6-fold elevated risk of bladder cancer compared with those with a low genetic risk and an optimal lifestyle (HR 3.63, 95% CI 2.23 -5.91).ConclusionsAdhering to a healthy lifestyle could substantially reduce the bladder cancer risk across all genetic strata, even for high-genetic risk individuals. For all populations, adopting an intermediate lifestyle is more beneficial than a poor one, and adhering to an optimal lifestyle is the ideal effective strategy for bladder cancer prevention.
| S-EPMC10568887 | biostudies-literature
Project description:BackgroundMidlife cardiovascular risk factors (CVRFs) increase risk of dementia. Black Americans experience an elevated prevalence of CVRFs and dementia. However, little is known of how CVRFs prior to midlife affect late-life cognition. We examined CVRFs in adolescence, young adulthood, and midlife with late-life cognition in the Study of Healthy Aging in African Americans (STAR).MethodSTAR assesses cognitive aging among 764 Black Americans aged ≥50 (mean age = 69; SD = 9; range = 53-95). Participants' body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Checkups (MHC; 1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRFs and cognition adjusting for demographics and years since MHC.ResultsAt MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (age 12-20), 62% young adults (age 21-34), and 16% midlife adults (age 35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function (β [95% CI]: -0.14 [-0.28, -0.0003]) and verbal episodic memory (β [95% CI]: -0.22 [-0.37, -0.07]) compared to normotension. Diabetes was associated with worse executive function (β [95% CI]: -0.43 [-0.83, -0.03]). Having ≥2 CVRFs (vs 0) was associated with worse executive function (β [95% CI]: -0.19 [-0.34, -0.03]) and verbal episodic memory (β [95% CI]: -0.25 [-0.41, -0.08]). Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents (β [95% CI]: -0.39 [-0.67, -0.11]). Young adulthood hypertension (β [95% CI]: -0.29 [-0.49, -0.09]) and midlife hyperlipidemia (β [95% CI]: -0.386 [-0.70, -0.02]) were associated with lower verbal episodic memory.ConclusionsAmong Black Americans, life-course CVRFs were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.
| S-EPMC8361347 | biostudies-literature