Objective: To determine the relative risk (RR) and cumulative incidenc
e of idiopathic Parkinson's disease (PD) in first-degree relatives of
PD patients compared with relatives of controls from the same geograph
ic region. Design: A family history questionnaire was used to obtain i
nformation on all first-degree relatives of cases and controls. A subs
et of these first-degree relatives was also examined. A Cox proportion
al hazards model with double-censoring techniques for missing informat
ion was used to model the RR for PD, adjusting for gender, ethnicity,
and relationship to proband. Results. A total of 1,458 first-degree re
latives of 233 PD patients were 2.3 times as likely (95% CI = 1.3 to 4
.0) as 7,834 relatives of 1,172 controls to develop PD. The cumulative
incidence of PD to age 75 among first-degree relatives of PD patients
was 2% compared with 1% among first-degree relatives of controls. The
risk in male first-degree relatives was higher than in female relativ
es (RR = 2.0, 95% CI = 1.1 to 3.4) and the risk in relatives of Caucas
ians was higher than in African-Americans and Hispanics (RR = 2.4, 95%
CI = 1.4 to 4.1). Risk for siblings and parents of probands was simil
ar. Conclusions: Susceptibility to PD is increased in first-degree rel
atives of both sporadic and familial cases. The pattern of inheritance
and the relationship between genetic and environmental risk factors w
arrant further study.