Joint Exposure to Multiple Air Pollutants, Genetic Susceptibility, and Incident Dementia: A Prospective Analysis in the UK Biobank Cohort.
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ABSTRACT:
SUBMITTER: Zhang S
PROVIDER: S-EPMC10901982 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
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Joint Exposure to Multiple Air Pollutants, Genetic Susceptibility, and Incident Dementia: A Prospective Analysis in the UK Biobank Cohort.
Zhang Shuo S Cao Hongyan H Chen Keying K Gao Tongyu T Zhao Huashuo H Zheng Chu C Wang Ting T Zeng Ping P Wang Ke K
International journal of public health 20240215
<b>Objectives:</b> This study aimed to evaluate the joint effects of multiple air pollutants including PM<sub>2.5</sub>, PM<sub>10</sub>, NO<sub>2</sub>, and NO<sub>x</sub> with dementia and examined the modifying effects of genetic susceptibility. <b>Methods:</b> This study included 220,963 UK Biobank participants without dementia at baseline. Weighted air pollution score reflecting the joint exposure to multiple air pollutants were constructed by cross-validation analyses, and inverse-variance ...[more]
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| S-EPMC8060055 | biostudies-literature
Project description:BackgroundAir pollution may cause inflammatory and oxidative stress damage to the brain, leading to neurodegenerative disease. The association between air pollution and dementia, and modification by apolipoprotein E genotype 4 (APOE-ε4) has yet to be fully investigated.ObjectivesTo examine associations of air pollution with three types of incident dementias (Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VAD)), and their potential modification by APOE-ε4 genotype.MethodsThe UK Biobank enrolled >500,000 participants (2006-2010) with ongoing follow-up. We used annual averages of air pollution (PM2.5, PM10, PM2.5-10, PM2.5absorbance, NO2, NOX) for 2010 scaled to interquartile ranges (IQR). We included individuals aged ≥60 years, with no dementia diagnosis prior to January 1, 2010. Time to incident dementia and follow-up time were reported from baseline (January 01, 2010) to last censor event (death, last hospitalization, or loss to follow-up). Cox proportional hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to estimate the association of air pollutants and incident dementia, and modification of these associations by APOE-ε4.ResultsOur sample included 187,194 individuals (including N = 680 AD, N = 377 VAD, N = 63 FTD) with a mean follow-up of 7.04 years. We observed consistent associations of PM2.5 with greater risk of all-cause dementia (HR = 1.17, 95% CI: 1.10, 1.24) and AD (HR = 1.17, 95% CI: 1.06, 1.29). NO2 was also associated with greater risk of any incident dementia (HR = 1.18, 95% CI: 1.10, 1.25), AD (HR = 1.15, 95% CI: 1.04, 1.28) and VAD (HR = 1.18, 95% CI: 1.03, 1.35). APOE-ε4 did not modify the association between any air pollutants and dementia.DiscussionPM2.5 and NO2 levels were associated with several types of dementia, and these associations were not modified by APOE-ε4. Findings from the UK Biobank support and extend to other epidemiological evidence for the potential association of air pollutants with detrimental brain health during aging.
| S-EPMC8976829 | biostudies-literature
Project description:BackgroundAir pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship.Methods and findingsA total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m2. Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM2.5), between 2.5 μm and 10 μm (PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants.ConclusionsWe found that various air pollutants PM2.5, PM2.5-10, NO2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.
| S-EPMC8439461 | biostudies-literature
Project description:BackgroundEvidence for a potential link between air pollution and rheumatoid arthritis (RA) is inconsistent, and the modified effect of genetic susceptibility on the relationship between air pollution and RA has not been well studied.ObjectiveUsing a general population cohort from the UK Biobank, this study aimed to investigate the associations between various air pollutants and the risk of incident RA and to further estimate the impact of combined exposure to ambient air pollutants on the risk of developing RA under the modification effect of genetic predisposition.MethodsA total of 342,973 participants with completed genotyping data and who were free of RA at baseline were included in the study. An air pollution score was constructed by summing the concentrations of each pollutant weighted by the regression coefficients with RA from single-pollutant models to assess the combined effect of air pollutants, including particulate matter (PM) with diameters ≤2.5μm (PM2.5), between 2.5 and 10μm (PM2.5-10), and ≤10μm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). In addition, the polygenic risk score (PRS) of RA was calculated to characterize individual genetic risk. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of associations of single air pollutant, air pollution score, or PRS with incident RA.ResultsDuring a median follow-up time of 8.1 y, 2,034 incident events of RA were recorded. The HRs (95% CIs) of incident RA per interquartile range increment in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.07 (1.01, 1.13), 1.00 (0.96, 1.04), 1.01 (0.96, 1.07), 1.03 (0.98, 1.09), and 1.07 (1.02, 1.12), respectively. We also found a positive exposure-response relationship between air pollution score and RA risk (pTrend=0.000053). The HR (95% CI) of incident RA was 1.14 (1.00, 1.29) in the highest quartile group compared with the lowest quartile group of the air pollution score. Furthermore, the results of the combined effect of air pollution score and PRS on the RA risk showed that the risk of RA incidence in the highest genetic risk and air pollution score group was almost twice that of the lowest genetic risk and air pollution score group [incidence rate (IR) per 100,000 person-years: 98.46 vs. 51.19, and HR= 1.73 (95% CI: 1.39, 2.17) vs. 1 (reference)], although no statistically significant interaction between the air pollution and genetic risk for incident RA was found (pInteraction>0.05).DiscussionThe results revealed that long-term combined exposure to ambient air pollutants might increase the risk of RA, particularly in those with high genetic risk. https://doi.org/10.1289/EHP10710.
| S-EPMC10010395 | biostudies-literature
Project description:BackgroundAccelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease.MethodsWe included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales.ResultsThese findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale.ConclusionsAccelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.
| S-EPMC11443929 | biostudies-literature
Project description:ObjectivesThere is paucity of studies to investigate the association between combined and long-term exposure to air pollution and the risk of incident chronic kidney disease (CKD) in older adults.MethodsA prospective cohort of 90,032 older adults who did not have CKD at baseline were followed up from January 1, 2017, to December 31, 2019. Various pollutant data, including particulate matter with diameters ≤ 2.5 mm (PM2.5), ≤ 10 mm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), Ozone (O3), and carbon monoxide (CO), from all monitoring stations in Binhai New Area, Tianjin were considered in calculating the mean exposure concentration of each pollutant over 2 years. By summing each pollutant concentration weighted by the regression coefficients, we developed an air pollution score that assesses the combined exposure of these air pollutants. Due to the strong correlation between air pollutants, Principal Component Analysis (PCA) score was also developed. The association between air pollutants and incident CKD in the elderly was analyzed.ResultsA total of 90,032 subjects participated in this study with a median follow-up of 545 days. Among them, 22,336 (24.8%) developed CKD. The HR (95% CI) for air pollution score and incidence of CKD was 1.062 (1.060-1.063) and p <0.001 after adjusting for all confounders. The adjusted HRs for the quartile subgroups of combined air pollution score were: Q2: 1.064 (1.013-1.117); Q3: 1.141 (1.088-1.198); and Q4: 3.623 (3.482-3.770), respectively (p for trend <0.001). The adjusted HRs for the quartile subgroups of air quality index (AQI) were: Q2: 1.035 (0.985-1.086); Q3: 1.145 (1.091-1.201); and Q4: 3.603 (3.463-3.748), respectively (p for trend <0.001). When the risk score was over 86.9, it significantly rose in a steep curve. The subgroup analysis showed that male, younger or exercise were more likely to develop CKD.ConclusionCombined air pollution score, AQI, and PCA score were associated with an increased risk of CKD in an exposure-response relationship. Our current results might also provide evidence for developing environmental protection policies.
| S-EPMC9524146 | biostudies-literature
Project description:BackgroundReproductive risk factors and air pollution for developing chronic obstructive pulmonary disease (COPD) have been documented separately. However, the combined effects of overall reproductive risk status on COPD and the extent to which this can be impacted by air pollution are unknown. The aim of this study was to construct a reproductive risk score (RRS) and an air pollution score (APS) and assess independent and joint associations between the two with incident COPD risk.Methods78,027 female participants aged 40-69 years without baseline COPD from UK Biobank recruited between 2006 to 2010 were included in this study. RRS was constructed by 17 women's reproductive health-related items, and APS incorporating PM2.5, PM2.5-10, PM10, NO2, and NOx was calculated to assess the joint exposure level. The outcome of the incident COPD was identified through the in-patient hospital register. The associations of RRS and APS with COPD were examined by Cox proportional hazards regression.ResultsThe risk of COPD reached its highest in the fourth quartile of the RRS (adjusted HR: 2.23, 95% CI: 1.76-2.82, P for trend < 0.001). A dose-response manner can also be observed between higher tertile APS with increased COPD risk and the highest risk was found in the third tertile of the APS (adjusted HR: 1.37, 95% CI: 1.19-1.58, P for trend < 0.001). The relative excess risk due to interaction (RERI) of 0.030 (95% CI: 0.012-0.048) showed additive interaction between RRS and APS on COPD was significant. In the joint analysis, the combinations of both higher RRS and APS signified higher incident COPD risk.ConclusionHigh RRS and high APS were jointly associated with increased COPD risks in a dose-response pattern. Using comprehensive indicators to identify women's reproductive risk factors, together with the control of air pollution, is effective for COPD prevention.
| S-EPMC10711373 | biostudies-literature
Project description:BackgroundUnraveling gene-environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population.ObjectiveWe investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence.MethodsThis study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution (PM2.5, PM10, NO2, and NOx) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales.ResultsAmong 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for PM2.5, 1.20 (95% CI: 1.19, 1.22) for PM10, 1.13 (95% CI: 1.12, 1.15) for NO2, and 1.12 (95% CI: 1.11, 1.13) for NOx. In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants (∼255% to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI.DiscussionThere were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291.
| S-EPMC11466320 | biostudies-literature
Project description:BackgroundFlooding has emerged as the most prevalent natural disaster, impacting billions of individuals worldwide. However, the long-term effects of flooding exposure on dementia remain unclear.MethodsWith a nested case-control design, a risk-set sampling method was used to match cases and controls. Annual cumulative flooding exposure was calculated for each participant. The associations between flooding exposure and incident dementia were assessed using conditional logistic regression models.ResultsHere we show that the risk of flood-related incident dementia is the strongest in the current year and diminished over a span of 6 years. In the fully adjusted model, the cumulative odds ratios (OR) are 1.28 (95% confidence interval [CI]: 1.25-1.31) for any dementia, 1.44 (95% CI: 1.36-1.53) for Alzheimer's disease and 1.65 (95% CI: 1.48-1.83) for vascular dementia, associated with per unit increase in annual cumulative flooding exposure over lag 0-6 years. Participants under the age of 65 years (OR: 1.39, 95% CI: 1.33-1.46) and female participants (OR: 1.41, 95% CI: 1.33-1.49) exhibit a higher risk of incident dementia compared to those aged 65 years and older (OR: 1.25, 95% CI: 1.21-1.28) and male participants (OR: 1.26, 95% CI: 1.23-1.30), respectively. Similar effect estimates are observed in the stratified analyses of Alzheimer's disease according to genetic factors.ConclusionsThis study provides robust epidemiological evidence supporting the link between floods and an increased risk of dementia. These findings enhance the understanding of the long-term consequences of flood exposure.
| S-EPMC11894203 | biostudies-literature
Project description:BackgroundWe aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities.MethodsWe recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure.ResultsDuring an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions.ConclusionsOsteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.
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