Abstract
An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population.
Highlights
Introduction to Epidemiologic ThinkingIn Epidemiology: An Introduction New York: Oxford University Press, Inc; 2002:5-6.4
The findings previously reported for multivitamin use and pack-years of smoking associated with later age-at-onset of PD are examples of the difficulty of studying associations between non-genetic risk factors and age-at-onset
The results presented here cast considerable doubt that a valid relation exists between multivitamin use, coffee drinking, or cigarette smoking and age-at-onset of PD
Summary
Studies of the relation between a risk factor and age-atonset of a disease, as opposed to the relation between a risk factor and the occurrence of disease, are designed to investigate the hypothesis that the risk factor causes the disease to occur earlier than it would have occurred without exposure to the risk factor. The GenePD study previously reported an association between a history of head trauma and younger age of PD onset, and associations between the use of multivitamins and greater pack-years of smoking with older ageat-onset [21]. The findings previously reported for multivitamin use and pack-years of smoking associated with later age-at-onset of PD are examples of the difficulty of studying associations between non-genetic risk factors and age-at-onset. Restricting the users to those who initiated multivitamin use at the youngest ages showed an association with earlier onset age This difference likely reflects a birth cohort effect because younger cases, born in more recent health conscious years, were more likely to use multivitamins before onset of PD compared to the group of cases who were never users of multivitamins. The direction and estimate of the effect size between the GenePD Study and the FHS sample are comparable, with substantially overlapping 95% confidence intervals
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
