Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study.
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SUBMITTER: Zhang N
PROVIDER: S-EPMC8217565 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionSmoking and genetic predisposition are established risk factors for colorectal cancer (CRC). We aimed to assess and compare their individual and joint impact on CRC risk using the novel approach of genetic risk equivalent (GRE).MethodsData were extracted from the Darmkrebs: Chancen der Verhütung durch Screening study, a large population-based case-control study in Germany. A polygenic risk score (PRS) based on 140 CRC-related single nucleotide polymorphisms was derived to quantify genetic risk. Multiple logistic regression was used to estimate the individual and joint impact of smoking and PRS on CRC risk, and to quantify the smoking effect in terms of GRE, the corresponding effect conveyed by a defined difference in PRS percentiles.ResultsThere were 5,086 patients with CRC and 4,120 controls included. Current smokers had a 48% higher risk of CRC than never smokers (adjusted odds ratio 1.48, 95% confidence interval 1.27-1.72). A PRS above the 90th percentile was significantly associated with a 3.6-, 4.3-, and 6.4-fold increased risk of CRC in never, former, and current smokers, respectively, when compared with a PRS below the 10th percentile in never smokers. The interaction between smoking and PRS on CRC risk did not reach statistical significance (P = 0.53). The effect of smoking was equivalent to the effect of having a 30 percentile higher level of PRS (GRE 30, 95% confidence interval 18-42).DiscussionBoth smoking and the PRS carry essentially independent CRC risk information, and their joint consideration provides powerful risk stratification. Abstinence from smoking can compensate for a substantial proportion of genetically determined CRC risk.
| S-EPMC7925134 | biostudies-literature
Project description:The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants1,2. Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia3. Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.
| S-EPMC6739225 | biostudies-literature
Project description:INTRODUCTION Smoking behavior can change with time and lead to different health outcomes. This study explored the trajectory of smoking and its relationship with cancer incidence and mortality among Korean male adults. METHODS We used 2002–2018 data from the National Health Insurance Service (NHIS). Smoking status was repeatedly measured in four waves of general health examinations provided by the NHIS between 2002 and 2009. Cancer incidence and mortality were tracked from 2010 to 2018. Trajectory analysis was used to identify the patterns of smoking. The hazard ratio was calculated using Cox proportional regression models. RESULTS For the 2448548 men (≥20 years), 137788 cases of cancers and 41146 cancer deaths were found. We identified six trajectory groups: never smokers, former smokers, new current smokers, decreasing light smokers, steady moderate smokers, and steady heavy smokers. All smoking groups had an increased risk of cancer. The steady heavy smokers showed higher cancer incidence and mortality rate than the steady non-smokers (hazard ratio, HR=1.53; 95% CI: 1.49–1.58 and HR=2.64; 95% CI: 2.50–2.79, respectively). The cancer-specific analysis showed that the larynx and lung cancer incidence and mortality rate of the smoking group were higher than in never smokers. CONCLUSIONS Smoking, even at low doses, increases the risk of most cancers in men. Quitting or reducing smoking, especially at a young age, can lower cancer incidence and mortality. This study may provide more objective results on the relationship between smoking and cancer, because smoking behavior was examined at multiple time points.
| S-EPMC9413414 | biostudies-literature
Project description:ObjectiveWe aimed to examine the associations of obesity-related traits (body mass index [BMI], central obesity) and their genetic predisposition with the risk of developing severe COVID-19 in a population-based data.Research design and methodsWe analyzed data from 489,769 adults enrolled in the UK Biobank-a population-based cohort study. The exposures of interest are BMI categories and central obesity (e.g., larger waist circumference). Using genome-wide genotyping data, we also computed polygenic risk scores (PRSs) that represent an individual's overall genetic risk for each obesity trait. The outcome was severe COVID-19, defined by hospitalization for laboratory-confirmed COVID-19.ResultsOf 489,769 individuals, 33% were normal weight (BMI, 18.5-24.9 kg/m2), 43% overweight (25.0-29.9 kg/m2), and 24% obese (≥30.0 kg/m2). The UK Biobank identified 641 patients with severe COVID-19. Compared to adults with normal weight, those with a higher BMI had a dose-response increases in the risk of severe COVID-19, with the following adjusted ORs: for 25.0-29.9 kg/m2, 1.40 (95%CI 1.14-1.73; P = 0.002); for 30.0-34.9 kg/m2, 1.73 (95%CI 1.36-2.20; P < 0.001); for 35.0-39.9 kg/m2, 2.82 (95%CI 2.08-3.83; P < 0.001); and for ≥40.0 kg/m2, 3.30 (95%CI 2.17-5.03; P < 0.001). Likewise, central obesity was associated with significantly higher risk of severe COVID-19 (P < 0.001). Furthermore, larger PRS for BMI was associated with higher risk of outcome (adjusted OR per BMI PRS Z-score 1.14, 95%CI 1.05-1.24; P = 0.004).ConclusionsIn this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19.
| S-EPMC7442576 | biostudies-literature
Project description:BACKGROUND:In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice. METHODS AND FINDINGS:The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ?50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5-5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56-2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding. CONCLUSIONS:In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia.
| S-EPMC6363148 | biostudies-literature
Project description:BackgroundImmunity has been suggested to be important in the pathogenesis of dementia. However, the contribution of innate versus adaptive immunity in the development of dementia is not clear. In this study, we aimed to investigate (1) the association between components of innate immunity (granulocytes and platelets) and adaptive immunity (lymphocytes) with risk of dementia and (2) the association between their derived ratios (granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and systemic immune-inflammation index [SII]), reflecting the balance between innate and adaptive immunity, with risk of dementia.MethodsBlood cell counts were measured repeatedly between 2002 and 2015 in dementia-free participants of the prospective population-based Rotterdam Study. Participants were followed-up for dementia until 1 January 2016. Joint models were used to determine the association between granulocyte, platelets, and lymphocyte counts, and their derived ratios with risk of dementia.ResultsOf the 8313 participants (mean [standard deviation] age 61.1 [7.4] years, 56.9% women), 664 (8.0%) developed dementia during a median follow-up of 8.6 years. Doubling of granulocyte and platelet counts tended to be associated with an increased risk of dementia (HR [95%CI] 1.22 [0.89-1.67] and 1.45 [1.07-1.95], respectively). Doubling of the derived ratios GLR, PLR, and SII were all associated with an increased dementia risk (HR [95%CI] 1.26 [1.03-1.53], 1.27 [1.05-1.53], and 1.15 [0.98-1.34], respectively).ConclusionsGLR, PLR, and SII are associated with an increased risk of dementia in the general population. This supports the role of an imbalance in the immune system towards innate immunity in the pathogenesis of dementia.
| S-EPMC6441146 | biostudies-literature
Project description:BACKGROUND:Former studies on smoking as a risk factor for Philadelphia-negative myeloproliferative neoplasms (MPNs) have mainly been carried out in women's cohorts and studies with various definitions of MPNs. Herein, we conducted a cohort study with register-based follow-up of a general population from Denmark, to validate and substantiate prior observations. METHODS:In the Danish Health Examination Survey cohort, we used the Cox proportional-hazards model adjusted for age, sex, body mass index, and level of education, to calculate hazard ratios (HRs), to investigate, whether daily smokers or occasional/ex-smokers had an increased risk of MPNs compared to never-smokers. RESULTS:From the time of data collection (September 2007 to October 2008) until 1 January 2015, 70 individuals were diagnosed with MPNs among 75 896 study participants. Similar results were observed in both the age and sex adjusted analysis and the multivariable analysis. The multivariable HR of any MPN diagnosis for daily smokers was 2.5 (95% CI: 1.3-5.0). For essential thrombocytosis, polycythemia vera, myelofibrosis, and MPN-unclassified, the HRs were 1.8 (95% CI: 0.5-5.8), 1.7 (95% CI: 0.5-5.8), 4.3 (95% CI: 0.9-19), and 6.2 (95% CI: 1.5-25), respectively. Among occasional/ex-smokers the corresponding HRs were 1.9 (95% CI: 1.1-3.3), 1.5 (95% CI: 0.6-3.7), 0.8 (95% CI: 0.3-2.4), 0.9 (95% CI: 0.2-4.4), and 6.2 (95% CI: 1.8-21). Participants, who smoked >15 g/day, had an overall HR of 3.4 (95% CI: 1.4-8.2) for any MPN diagnosis, while participants who smoked ?15 g/day, had an overall HR of 2.1 (95% CI: 0.9-4.7). CONCLUSION:Smoking was associated with MPN development when comparing smokers and never-smokers. Further studies investigating smoking in MPNs are warranted to substantiate our findings.
| S-EPMC6246929 | biostudies-other
Project description:BACKGROUND:More children with congenital heart disease (CHD) are surviving to adulthood, and CHD is associated with risk factors for dementia. We compared the risk of dementia in CHD adults to that of the general population. METHODS:In this cohort study, we used medical registries and a medical record review covering all Danish hospitals to identify adults with CHD diagnosed between 1963 and 2012. These individuals with CHD were followed from January 1, 1981, 30 years of age, or date of first CHD registration (index date for matched members of the general population cohort) until hospital diagnosis of dementia, death, emigration, or end of study (December 31, 2012). For each individual with CHD, we identified 10 members of the general population utilizing the Danish Civil Registration System matched on sex and birth year. We computed cumulative incidences and hazard ratios (HRs) of dementia, adjusting for sex and birth year. RESULTS:The cumulative incidence of dementia was 4% by 80 years of age in 10?632 adults with CHD (46% male). The overall HR comparing adults with CHD with the general population cohort was 1.6 (95% confidence interval [CI], 1.3-2.0). The HR among individuals with CHD without extracardiac defects was 1.4 (95% CI, 1.1-1.8). Adults with mild-to-moderate CHD had an HR of 1.5 (95% CI, 1.1-2.0), whereas the HR was 2.0 (95% CI, 1.2-3.3) for severe CHD, including univentricular hearts. The HR for early onset dementia (<65 years of age) was 2.6 (95% CI, 1.8-3.8), whereas the late-onset HR was 1.3 (95% CI, 1.0-1.8). CONCLUSIONS:CHD was associated with an increased risk of dementia compared with the general population, in particular for early onset dementia. Further understanding of dementia risk in the population with CHD is a potential target for future investigation.
| S-EPMC5930034 | biostudies-literature
Project description:Dementia is one of the most burdensome illnesses in elderly populations worldwide. However, the literature about multiple risk factors for dementia is scant.To develop a simple, rapid, and appropriate predictive tool for the clinical quantitative assessment of multiple risk factors for dementia.A population-based cohort study.Based on the Taiwan National Health Insurance Research Database, participants first diagnosed with dementia from 2000 to 2009 and aged ?65 years in 2000 were included.A logistic regression model with Bayesian supervised learning inference was implemented to evaluate the quantitative effects of 1- to 6-comorbidity risk factors for dementia in the elderly Taiwanese population: depression, vascular disease, severe head injury, hearing loss, diabetes mellitus (DM), and senile cataract, identified from a nationwide longitudinal population-based database.This study enrolled 4749 (9.5%) patients first diagnosed as having dementia. Aged, female, urban residence, and low income were found as independent sociodemographic risk factors for dementia. Among all odds ratios (ORs) of 2-comorbidity risk factors for dementia, comorbid depression and vascular disease had the highest adjusted OR of 6.726. The 5-comorbidity risk factors, namely depression, vascular disease, severe head injury, hearing loss, and DM, exhibited the highest OR of 8.767. Overall, the quantitative effects of 2 to 6 comorbidities and age difference on dementia gradually increased; hence, their ORs were less than additive. These results indicate that depression is a key comorbidity risk factor for dementia.The present findings suggest that physicians should pay more attention to the role of depression in dementia development. Depression is a key cormorbidity risk factor for dementia. It is the urgency of evaluating the nature of the link between depression and dementia; and further testing what extent controlling depression could effectively lead to the prevention of dementia.
| S-EPMC5908585 | biostudies-literature
Project description:AimsThe association between heart failure and dementia remains unclear. We assessed the risk of dementia among patients with heart failure and members of a general population comparison cohort.Methods and resultsIndividual-level data from Danish medical registries were linked in this nationwide population-based cohort study comparing patients with a first-time hospitalization for heart failure between 1980 and 2012 and a year of birth-, sex-, and calendar year-matched comparison cohort from the general population. Stratified Cox regression analysis was used to compute 1-35-year hazard ratios (HRs) for the risk of all-cause dementia and, secondarily, Alzheimer's disease, vascular dementia, and other dementias. Analyses included 324 418 heart failure patients and 1 622 079 individuals from the general population (median age 77 years, 52% male). Compared with the general population cohort, risk of all-cause dementia was increased among heart failure patients [adjusted HR 1.21, 95% confidence interval (CI) 1.18-1.24]. The associations were stronger in men and in heart failure patients under age 70. Heart failure patients had higher risks of vascular dementia (adjusted HR 1.49, 95% CI 1.40-1.59) and other dementias (adjusted HR 1.30, 95% CI 1.26-1.34) than members of the general population cohort. Heart failure was not associated with Alzheimer's disease (adjusted HR 1.00, 95% CI 0.96-1.04).ConclusionHeart failure was associated with an increased risk of all-cause dementia. Heart failure may represent a risk factor for dementia, but not necessarily for Alzheimer's disease.
| S-EPMC5522185 | biostudies-literature