Correspondence

Familial Aggregation of Parkinson's Disease

N Engl J Med 2001; 344:1168April 12, 2001

Article

To the Editor:

The observations in the report by Sveinbjörnsdóttir et al. (Dec. 14 issue)1 are important, but we believe they support a predominantly environmental cause rather than a major genetic contribution to the etiology of Parkinson's disease.

Figure 1 of the article is a clear example of horizontal rather than vertical clustering, which suggests environmental causation. As the authors recognize, the fact that the risk ratio for Parkinson's disease in the siblings of patients with Parkinson's disease was different from the risk ratio in the offspring of such patients also argues against genetic causation. The relative risk of Parkinson's disease was similar for offspring and for nephews and nieces of patients with late-onset Parkinson's disease (risk ratios, 3.2 and 2.7, respectively), which, again, is not in keeping with a genetic cause. Indeed, the observations suggest the existence of two cohorts defined according to the calendar year of their birth who had similar environmental exposure.

The findings offer rather strong support for the hypothesis that shared environmental factors early in life are likely to have a crucial role in causing most cases of Parkinson's disease. As the authors acknowledge, the findings are inconsistent with the view that Parkinson's disease derives directly from gene mutations,2 but heterozygous highly prevalent abnormalities in a recessive gene such as parkin 3 could certainly increase susceptibility to environmental risk factors.

Raúl de la Fuente-Fernández, M.D.
Donald B. Calne, D.M.
University of British Columbia, Vancouver, BC V6T 2B5, Canada

3 References

1. 1

   Sveinbjornsdottir S, Hicks AA, Jonsson T, et al. Familial aggregation of Parkinson's disease in Iceland. N Engl J Med 2000;343:1765-1770
   Full Text | Web of Science | Medline

2. 2

   de la Fuente-Fernandez R. Maternal effect on Parkinson's disease. Ann Neurol 2000;48:782-787
   CrossRef | Web of Science | Medline

3. 3

   Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998;392:605-608
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree with Fuente-Fernández and Calne that our data are consistent with the contribution of an environmental component to the risk of Parkinson's disease. However, the data also show significant familial clustering extending beyond the nuclear family, strongly supporting the theory that there is also a genetic component. We believe that the isolation of the susceptibility gene, the identification of the variant that increases the risk of Parkinson's disease, and the determination of its function will lead to a better understanding of the contribution of the environment. Indeed, ignoring the genetic component of the disease will only complicate efforts to identify the relevant environmental factors.

Augustine Kong, Ph.D.
Sigurlaug Sveinbjörnsdóttir, M.D.
Kári Stefánsson, M.D., Ph.D.
deCODE Genetics, Reykjavik, Iceland

Citing Articles (2)

Citing Articles

1. 1

   Giancarlo Logroscino. (2005) The Role of Early Life Environmental Risk Factors in Parkinson Disease: What Is the Evidence?. Environmental Health Perspectives 113:9, 1234-1238
   CrossRef

2. 2

   Raúl de la Fuente-Fernández, Donald B Calne. (2002) Evidence for environmental causation of Parkinson's disease. Parkinsonism & Related Disorders 8:4, 235-241
   CrossRef