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No evidence for heritability of Parkinson disease in Swedish twins

From the Departments of Medical Epidemiology and Biostatistics (Drs. Wirdefeldt, Gatz, and Pedersen) and Molecular Medicine (Dr. Schalling), Karolinska Institutet, Stockholm, Sweden; and Department of Psychology (Drs. Gatz and Pedersen), University of Southern California, Los Angeles.

Address correspondence and reprint requests to Dr. N.L. Pedersen, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden; e-mail: Nancy.Pedersen{at}meb.ki.se

Background: Although several genes are implicated in Parkinson disease (PD), they explain only a small fraction of cases. The etiology of most cases is yet unknown.

Objective: To evaluate heritability of PD in same-sexed and opposite-sexed twin pairs in the Swedish Twin Registry (STR).

Methods: All twins in the STR born in 1950 or earlier and alive in 1998 (n = 50,150) were included. The authors screened 33,780 twins in 14,082 pairs for PD by telephone interviews and linked the STR to the Swedish Inpatient Discharge Register. Two hundred forty-seven twins with self-reported PD or a PD diagnosis in the Inpatient Discharge Register (called "possible PD") and 517 twins who reported parkinsonian symptoms or use of antiparkinsonian medication ("suspected parkinsonism or movement disorder") were identified.

Results: For possible PD, there were only two concordant pairs, both female dizygotic. Similarly, concordances were low in all zygosity groups when the definition of affected was expanded to include twins with suspected parkinsonism or movement disorder in addition to possible PD. Sex differences in the relative importance of genetic and environmental effects were indicated with a marginally larger familial component in women. The best-fitting structural equation model included only environmental components of variance.

Conclusions: These results suggest that environmental factors are most important in the etiology of PD. Compared with other complex diseases, the importance of genetic effects in PD is notably low. The preponderance of discordant twin pairs provides an ideal material for studying environmental risk factors and potential genotype-by-environment interaction.

Received November 26, 2003. Accepted in final form March 16, 2004.

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