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:BackgroundAlthough genetic factors are known to play a role in the pathogenesis of bladder cancer, population-level familial risk estimates are scarce. We aimed to quantify the familial risk of bladder cancer and analyze interactions between family history and smoking or alcohol consumption.MethodsUsing the National Health Insurance database, we constructed a cohort of 5,524,403 study subjects with first-degree relatives (FDRs) and their lifestyle risk factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (CIs) that compare the risk of individuals with and without affected FDRs. Interactions between family history and smoking or alcohol intake were assessed on an additive scale using the relative excess risk due to interaction (RERI).ResultsOffspring with an affected parent had a 2.09-fold (95% CI: 1.41 - 3.08) increased risk of disease compared to those with unaffected parents. Familial risks of those with affected father and mother were 2.26 (95% CI: 1.51 - 3.39) and 1.10 (95% CI: 0.27 - 4.41), respectively. When adjusted for lifestyle factors, HR reduced slightly to 2.04 (95% CI: 1.38 - 3.01), suggesting that a genetic predisposition is the main driver in the familial aggregation. Smokers with a positive family history had a markedly increased risk of disease (HR: 3.60, 95% CI: 2.27 - 5.71), which exceeded the sum of their individual risks, with statistically significant interaction (RERI: 0.72, 95% CI: 0.31 - 1.13). For alcohol consumption, drinkers with a positive family history also had an increased risk of disease, although the interaction was not statistically significant (RERI: 0.05, 95% CI: -3.39 - 3.48).ConclusionSmokers and alcohol consumers with a positive family history of bladder cancer should be considered a high-risk group and be advised to undergo genetic counseling.
| S-EPMC10588503 | 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:Dementia and Alzheimer's disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score-matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score-matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent (P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.
| S-EPMC8982009 | 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:The incidence rate of dementia varies between studies. The influence of some sociodemographic factors is reasonably established, but less is known about the role of comorbidities, which are common in the elderly. The objectives of this study was to estimate the incidence of dementia in a population of Italian elders and evaluate the role of walking speed, comorbidity and ApoE-ɛ4 as well as various sociodemographic factors on the new onset of dementia. The InveCe.Ab study is a population-based longitudinal study in people born between 1935 and 1939 and resident in Abbiategrasso, Milan, Italy. After excluding subjects with a diagnosis of dementia and those without a definite diagnosis, 1103 individuals with a median follow-up time of 4.1 years were included in the analyses. The cumulative four-year incidence of dementia was 5.3%. Demographic factors such as old age, male, less educated, ApoE-ɛ4 carrier status and slower gait were risk factors for dementia onset in a cognitively healthy sub-cohort. Comorbidity did not influence the onset of dementia; instead, slow walking speed appears to be a strong predictor of dementia onset.
| S-EPMC9315866 | 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