Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis: the GENEVA study. Rationale, study design and demographic characteristics.
Ontology highlight
ABSTRACT:
SUBMITTER: Schmidt S
PROVIDER: S-EPMC2645711 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundRecent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS).ObjectiveTo evaluate environmental and occupational exposures as risk factors for sporadic ALS.MethodsWe performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness.ResultsSelf-reported job- or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% CI 1.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status.ConclusionsOur study contributes to a growing body of literature implicating occupational- and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors.
| S-EPMC5383428 | biostudies-literature
Project description:BackgroundAmyotrophic lateral sclerosis (ALS) is a rare yet devastating neurodegenerative condition. The mechanisms leading to ALS are most certainly complex and likely involve a joint contribution of several factors with possible synergistic or antagonistic interactions. To provide a better understanding of the association between non-genetic factors and ALS, we evaluated the joint exposure to multiple health and environmental factors linked with ALS in our previous studies, also screening for high-dimensional interactions.MethodsWe used data from a nested case-control study within the Danish population, with 1086 ALS cases from 1982 to 2009, jointly investigating 4 hospital-based diagnoses - diabetes, obesity, physical/stress trauma, cardiovascular disease (CVD) during 1977-2009; and 4 environmental exposures - lead, formaldehyde, diesel exhaust, and solvents, assessed from individual occupational history. All covariates were evaluated as ever/never exposed, and we used targeted machine learning techniques to screen for important joint predictors and interactions. These were then evaluated in a final logistic regression model adjusting for potential confounders (age, SES, geography). All analyses were stratified by sex.ResultsAmong men, trauma and solvents were associated with higher odds of ALS (OR = 1.55, 95% CI: 1.08-2.23; OR = 1.49, 95% CI: 1.17-1.89, respectively), and presented a negative interaction (OR = 0.49, 95% CI: 0.30-0.80). A positive diesel/CVD interaction was observed (OR = 1.56, 95% CI: 0.94-2.60). Among women, solvents, trauma, lead, and CVD were associated with higher odds of ALS, and a negative lead/solvents interaction was documented (OR = 0.52, 95% CI: 0.42-0.63).ConclusionsThis study is one of the first attempts to evaluate joint and interactive effects of multiple risk factors on ALS, identifying potential synergistic and antagonistic mechanisms.
| S-EPMC7736520 | biostudies-literature
Project description:Sporadic Amyotrophic Lateral Sclerosis Study
| PRJNA310034 | ENA
Project description:OBJECTIVES:To examine the associations of specific occupations and occupational exposures with the risk of amyotrophic lateral sclerosis (ALS) in the Swedish population. METHODS:A nested case-control study was conducted in Sweden. Patients with ALS diagnosed during 1991-2010 (n=5020) were identified from the National Patient Register and 5 controls per case (n=25?100) were randomly selected from the general Swedish population, individually matched to cases by birth year and sex. Occupational history was obtained from the Swedish censuses in 1970, 1980 and 1990. The Nordic Occupational Cancer Study Job Exposure Matrix was used to identify exposures related to individual occupations. Conditional logistic regression was used to estimate ORs and their 95% CIs. RESULTS:Higher risk of ALS was associated with precision-tool manufacturing (OR 1.68, 95% CI 1.11 to 2.52) and glass, pottery and tile work (OR 1.76, 95% CI 1.03 to 3.00), whereas lower risk was associated with textile work (OR 0.44, 95% CI 0.21 to 0.91). None of the examined occupational exposures were associated with ALS risk overall. However, among individuals younger than 65?years of age, an association with a higher risk of ALS was found for formaldehyde (OR 1.29, 95% CI 1.00 to 1.65), and an association with a lower risk of ALS was found for methylene chloride (OR 0.49, 95% CI 0.26 to 0.93). CONCLUSIONS:We identified several occupations and occupational exposures that may be associated with the risk of ALS in Sweden. Occupational history obtained from censuses every 10?years remains a limitation of the study.
| S-EPMC5451107 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) may be associated with low body mass index (BMI) at the time of diagnosis. However, the role of premorbid BMI in the development of ALS and survival after diagnosis remains unclear. In 2005-2010, we interviewed 467 patients with ALS from the US National Registry of Veterans with ALS and 975 frequency-matched veteran controls. In this sample, we evaluated the association of BMI and BMI change at different ages with ALS risk using unconditional logistic models and with survival after ALS diagnosis using Cox proportional hazards models. After adjustment for confounders, compared with a moderate increase in BMI between ages 25 and 40 years, stable or decreasing BMI was positively associated with ALS risk (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.20, 2.16). A 1-unit increase in BMI at age 40 years (OR = 0.95, 95% CI: 0.91, 0.98) but not at age 25 years (OR = 0.99, 95% CI: 0.95, 1.03) was inversely associated with ALS. These associations were similar for bulbar and spinal ALS but stronger for those with a delay of less than 1 year between symptom onset and diagnosis. We found no association between prediagnosis BMI and survival. A decreasing BMI from early to middle age and a low BMI in middle age may be positively associated with ALS risk.
| S-EPMC5860019 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases.Significant advances have been made in unravelling the genetic susceptibility to ALS with massively parallel sequencing technologies, while environmental insults remain a suspected but largely unexplored source of risk. Several studies applying the strategy of Mendelian randomisation have strengthened the link between environmental insults and ALS, but none so far has proved conclusive. We propose a new ALS model which links the current knowledge of genetic factors, ageing and environmental insults. This model provides a mechanism as to how ALS is initiated, with environmental insults playing a critical role.The available evidence has suggested that inherited defect(s) could cause mitochondrial dysfunction, which would establish the primary susceptibility to ALS. Further study of the underlying mechanism may shed light on ALS pathogenesis. Environmental insults are a critical trigger for ALS, particularly in the aged individuals with other toxicant susceptible genes. The identification of ALS triggers could lead to preventive strategies for those individuals at risk.
| S-EPMC5472994 | biostudies-literature
Project description:ImportancePersistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).ObjectiveTo evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.Design, setting, and participantsCase-control study conducted between 2011 and 2014 at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive, probable, probable with laboratory support, or possible ALS by revised El Escorial criteria; controls were excluded if they were diagnosed as having ALS or another neurodegenerative condition or if they had a family history of ALS in a first- or second-degree blood relative. Participants completed a survey assessing occupational and residential exposures. Blood concentrations of 122 persistent environmental pollutants, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs), were measured using gas chromatography-mass spectrometry. Multivariable models with self-reported occupational exposures in various exposure time windows and environmental toxin blood concentrations were separately fit by logistic regression models. Concordance between the survey data and pollutant measurements was assessed using the nonparametric Kendall τ correlation coefficient.Main outcomes and measuresOccupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs, PCBs, and BFRs.ResultsParticipants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5% male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8% male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS (odds ratio [OR] = 5.09; 95% CI, 1.85-13.99; P = .002). Military service was also associated with ALS in 2 time windows (exposure ever happened in entire occupational history: OR = 2.31; 95% CI, 1.02-5.25; P = .046; exposure ever happened 10-30 years ago: OR = 2.18; 95% CI, 1.01-4.73; P = .049). A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.21; 95% CI, 1.06-4.60; P = .04; and cis-chlordane: OR = 5.74; 95% CI, 1.80-18.20; P = .005), 2 PCBs (PCB 175: OR = 1.81; 95% CI, 1.20-2.72; P = .005; and PCB 202: OR = 2.11; 95% CI, 1.36-3.27; P = .001), and 1 BFR (polybrominated diphenyl ether 47: OR = 2.69; 95% CI, 1.49-4.85; P = .001). There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood; significant Kendall τ correlation coefficients ranged from -0.18 (Dacthal and "use pesticides to treat home or yard") to 0.24 (trans-nonachlor and "store lawn care products in garage").Conclusions and relevanceIn this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk factors.
| S-EPMC5032145 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE39642: NanoString nCounter immune-related gene expression in blood sorted CD14+CD16- monocytes from sALS, fALS and HC subjects GSE39643: NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects Refer to individual Series
2012-07-25 | E-GEOD-39644 | biostudies-arrayexpress
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other
2003-11-14 | GSE833 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-07-26 | GSE39644 | GEO