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Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex.

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The purpose of this paper is to investigate and develop methods for analysis of multi-center randomized clinical trials which only rely on the randomization process as a basis of inference. Our motivation is prompted by the fact that most current statistical procedures used in the analysis of randomized multi-center studies are model based. The randomization feature of the trials is usually ignored.

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