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An Etiologic Study

Caroline M. Tanner, MD, PhD; Ruth Ottman, PhD; Samuel M. Goldman, MD, MPH; Jonas Ellenberg, PhD; Piu Chan, MD, PhD; Richard Mayeux, MSc, MD; J. William Langston, MD

JAMA. 1999;281:341-346.

Context  The cause of Parkinson disease (PD) is unknown. Genetic linkages have been identified in families with PD, but whether most PD is inherited has not been determined.

Objective  To assess genetic inheritance of PD by studying monozygotic (MZ) and dizygotic (DZ) twin pairs.

Design  Twin study comparing concordance rates of PD in MZ and DZ twin pairs.

Setting and Participants  A total of 19,842 white male twins enrolled in the National Academy of Sciences/National Research Council World War II Veteran Twins Registry were screened for PD and standard diagnostic criteria for PD were applied. Zygosity was determined by polymerase chain reaction or questionnaire.

Main Outcome Measure  Parkinson disease concordance in twin pairs, stratified by zygosity and age at diagnosis.

Results  Of 268 twins with suspected parkinsonism and 250 presumed unaffected twin brothers, 193 twins with PD were identified (concordance-adjusted prevalence, 8.67/1000). In 71 MZ and 90 DZ pairs with complete diagnoses, pairwise concordance was similar (0.129 overall, 0.155 MZ, 0.111 DZ; relative risk, 1.39; 95% confidence interval, 0.63-3.1). In 16 pairs with diagnosis at or before age 50 years in at least 1 twin, MZ concordance was 1.0 (4 pairs), and DZ was 0.167 (relative risk, 6.0; 95% confidence interval, 1.69-21.26).

Conclusions  The similarity in concordance overall indicates that genetic factors do not play a major role in causing typical PD. No genetic component is evident when the disease begins after age 50 years. However, genetic factors appear to be important when disease begins at or before age 50 years.

Author Affiliations: The Parkinson's Institute, Sunnyvale, Calif (Drs Tanner, Goldman, Chan, and Langston); Gertrude Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY (Drs Ottman and Mayeux); and Biometry and Field Studies, National Institute of Neurologic Disease and Stroke, National Institutes of Health, Bethesda, Md (Dr Ellenberg). Dr Ellenberg is now with Westat, Rockville, Md.

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