Familial aggregation of early‐ and late‐onset Parkinson's disease

The role of heredity in early‐ versus late‐onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first‐degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first‐degree relatives of 409 control probands. Risk of PD was similar among first‐degree relatives of early‐onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6–5.0; p = 0.0002) and late‐onset PD probands (RR, 2.7; 95% CI, 1.6–4.4; p = 0.0002) when each was compared with first‐degree relatives of controls. However, siblings of early‐onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5–25.5; p = 0.0005), whereas parents of early‐onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9–3.3; p = 0.2). In late‐onset families, both siblings (RR, 3.6; 95% CI, 1.3–10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4–4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late‐onset PD. Genetic factors are important in both early‐ and late‐onset PD, but specific genes and mode of inheritance may differ between the two groups. Ann Neurol 2003;54:507–513