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      Pesticide exposure and risk of Parkinson's disease: A family-based case-control study

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          Abstract

          Background

          Pesticides and correlated lifestyle factors (e.g., exposure to well-water and farming) are repeatedly reported risk factors for Parkinson's disease (PD), but few family-based studies have examined these relationships.

          Methods

          Using 319 cases and 296 relative and other controls, associations of direct pesticide application, well-water consumption, and farming residences/occupations with PD were examined using generalized estimating equations while controlling for age-at-examination, sex, cigarette smoking, and caffeine consumption.

          Results

          Overall, individuals with PD were significantly more likely to report direct pesticide application than their unaffected relatives (odds ratio = 1.61; 95% confidence interval, 1.13–2.29). Frequency, duration, and cumulative exposure were also significantly associated with PD in a dose-response pattern ( p ≤ 0.013). Associations of direct pesticide application did not vary by sex but were modified by family history of PD, as significant associations were restricted to individuals with no family history. When classifying pesticides by functional type, both insecticides and herbicides were found to significantly increase risk of PD. Two specific insecticide classes, organochlorines and organophosphorus compounds, were significantly associated with PD. Consuming well-water and living/working on a farm were not associated with PD.

          Conclusion

          These data corroborate positive associations of broadly defined pesticide exposure with PD in families, particularly for sporadic PD. These data also implicate a few specific classes of pesticides in PD and thus emphasize the need to consider a more narrow definition of pesticides in future studies.

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          Most cited references36

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          Longitudinal data analysis for discrete and continuous outcomes.

          Longitudinal data sets are comprised of repeated observations of an outcome and a set of covariates for each of many subjects. One objective of statistical analysis is to describe the marginal expectation of the outcome variable as a function of the covariates while accounting for the correlation among the repeated observations for a given subject. This paper proposes a unifying approach to such analysis for a variety of discrete and continuous outcomes. A class of generalized estimating equations (GEEs) for the regression parameters is proposed. The equations are extensions of those used in quasi-likelihood (Wedderburn, 1974, Biometrika 61, 439-447) methods. The GEEs have solutions which are consistent and asymptotically Gaussian even when the time dependence is misspecified as we often expect. A consistent variance estimate is presented. We illustrate the use of the GEE approach with longitudinal data from a study of the effect of mothers' stress on children's morbidity.
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            Association of Pesticide Exposure with Neurologic Dysfunction and Disease

            Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease.
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              Family-based designs in the age of large-scale gene-association studies.

              Both population-based and family-based designs are commonly used in genetic association studies to locate genes that underlie complex diseases. The simplest version of the family-based design--the transmission disequilibrium test--is well known, but the numerous extensions that broaden its scope and power are less widely appreciated. Family-based designs have unique advantages over population-based designs, as they are robust against population admixture and stratification, allow both linkage and association to be tested for and offer a solution to the problem of model building. Furthermore, the fact that family-based designs contain both within- and between-family information has substantial benefits in terms of multiple-hypothesis testing, especially in the context of whole-genome association studies.
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                Author and article information

                Journal
                BMC Neurol
                BMC Neurology
                BioMed Central
                1471-2377
                2008
                28 March 2008
                : 8
                : 6
                Affiliations
                [1 ]Center for Human Genetics, Duke University Medical Center, Durham, NC, USA
                [2 ]Department of Medicine, Duke University Medical Center, Durham, NC, USA
                [3 ]Miami Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
                Article
                1471-2377-8-6
                10.1186/1471-2377-8-6
                2323015
                18373838
                c33f982b-9c0f-4e8b-ba6b-1c194739fdae
                Copyright © 2008 Hancock et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 September 2007
                : 28 March 2008
                Categories
                Research Article

                Neurology
                Neurology

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