Table 1.
Bradford Hill viewpoints.
Table 2.
Number of studies assigned to each category (Tier 1, Tier 2, exposure interview technique, pesticide exposure assessment, source population, type of controls and adjustment for confounders) for each environmental or lifestyle risk factor.
Table 3.
Fixed and random effects meta-analysis relative risk (RR) estimates and their 95% confidence intervals (CIs) for the association between Parkinson’s disease and each risk factor based on Tier 1 studies and all studies combined.
Table 4.
Heterogeneity estimates for each risk factor based on between-study variance (τ2) among Tier 1, Tier 2 or Tiers 1&2 studies combined.
Fig 1.
Association between current cigarette smoking and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed. Current smokers have a significantly greater or lower risk of PD than non-smokers if the horizontal line for the study is to the right or to the left, respectively, of the bold vertical line [ln(RR) = 0] and does not cross it. PD risk for current smokers is similar to that in non-smokers if the horizontal line for the study crosses the bold vertical axis. An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval, HPFS = Health Professionals Follow-Up Study, M & F = males and females, NHS = Nurses’ Health Study, PD = Parkinson’s disease. Citations for studies appearing in this figure can be found here: [3, 18, 20, 60–95].
Fig 2.
Association between the heavy or long-term cigarette smoking and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval, M & F = males and females, PD = Parkinson’s disease. Citations for studies appearing in this figure can be found here: [18, 55, 59–62, 64–66, 68, 70, 71, 74, 75, 77, 80, 82, 84–88, 90, 91, 93, 95–111].
Table 5.
Weight-of-the-evidence assessment of causality based upon Bradford Hill viewpoints.
Fig 3.
Association between rural living and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [54, 56, 58, 59, 64, 76, 98–100, 102, 104, 114–130].
Fig 4.
Association between well-water consumption and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval, PD = Parkinson’s disease. Citations for studies appearing in this figure can be found here: [55, 58, 59, 63, 69, 79, 81, 83, 84, 99, 100, 102, 104, 114, 115, 117–137].
Fig 5.
Association between farming and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval, M & F = males and females. Citations for studies appearing in this figure can be found here: [19, 20, 55, 57–59, 63, 73, 79–81, 84, 87, 92, 104, 107, 114–116, 118, 121, 122, 124, 127–132, 134, 135, 137–156].
Fig 6.
Association between pesticide use and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [18, 19, 54–59, 68–70, 73, 79–81, 84, 87, 89, 91, 92, 94, 100, 102, 107, 114–116, 118, 120, 123, 125–130, 132, 134–137, 139–141, 143, 149–151, 154–158].
Fig 7.
Association between herbicide (Panel a), fungicide (Panel b) or insecticide use (Panel c) and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [55, 58, 80, 81, 92, 102, 104, 114, 115, 119, 121, 122, 132, 135, 137, 143, 155–158].
Fig 8.
Association between high herbicide (Panel a), high fungicide (Panel b) or high insecticide use (Panel c) and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [55, 81, 98, 115, 121, 130, 135, 143, 150].
Fig 9.
Association between ever use (Panel a) or high use (Panel b) of paraquat and Parkinson’s disease.
The natural logarithm of the estimated relative risk [ln(RR)] and the 95% confidence interval for each study are displayed (see the legend for Fig 1 for instructions on how to interpret forest plots). An asterisk (*) denotes RR estimates that are not included in the meta-analysis due to study overlap with another RR estimate shown in the figure. RR = relative risk, LCL = lower limit of the 95% confidence interval, UCL = upper limit of the 95% confidence interval. Citations for studies appearing in this figure can be found here: [18, 55, 57, 59, 68, 69, 81, 92, 114, 132, 135, 154, 156, 160–165].
Table 6.
Comparison of meta-analysis results from this study to results in the published literature1: meta-relative risk (RR; random effects model), 95 percent confidence interval (CI) and number of studies (N).
Table 7.
Conclusions from published systematic reviews and meta-analyses of epidemiology studies on Parkinson’s disease.