Genetic Determinants of Hair Color and Parkinson's Disease Risk

Objective: A history of melanoma is associated with increased risks for Parkinson's disease (PD). We examined whether hair color, one of the most important phenotypes of pigmentation and a risk factor for melanoma, was associated with PD risk in the Health Professionals Follow-up Study (HPFS; 1986-2002) and the Nurses' Health Stud), (NHS; 1980-2002). Methods: We included 38,641 men and 93,661 women who were free of PD at baseline. Information on natural hair color in early adulthood (age 18-21 years) was assessed via a questionnaire. We also conducted a case-control study (298 PD cases) nested in these two cohorts to examine the association between the melanocortin] -receptor Arg151Cys polymorphism and PD risk. Relative risks (RRs) were estimated using Cox proportional hazards models in the cohort analyses and conditional logistic regression in the nested case-control study. Results: PD risk increased with decreasing darkness of hair color. Pooled RRs for PD were I (reference), 1.40, 1.61, and 1.93 (95% confidence interval, 1.1-3.4) for black, brown, blond, and red hair, respectively, after adjusting for age, smoking, ethnicity, and other covariates. The associations between hair color and PD were particularly strong for relative younger onset of PD (< 70 yr) (adjusted RR for red vs black hair = 3.83; 95% confidence interval, 1.7-8.7). In the case-control study, participants with Cys/Cys genotype, which was associated with red hair, had a greater PD risk, relative to the Arg/Arg genotype (adjusted RR, 3.15; 95% confidence interval, 1.1-9.4). Interpretation: These findings suggest a potential role of pigmentation in PD.