Genetic determinants of hair color and parkinson's disease risk
Open accessAbstract
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 Study (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 melanocortin1‐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 1 (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. Ann Neurol 2009;65:76–82
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Light hair color and red hair MC1R alleles are risk factors for both melanoma and Parkinson's disease, and Parkinson's disease patients have a 7-fold elevated melanoma risk.
“Light hair color and the red hair alleles of the MC1R gene are risk factors for both melanoma and PD, while PD patients have a 7-fold elevated risk for melanoma (239, 240);”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [240]
The Discussion (page unavailable) reports higher Parkinson’s disease risk with lighter hair and the MC1R Arg151Cys variant; the paper also identifies both as melanoma risk factors. It does not report a sevenfold melanoma risk in patients with Parkinson’s disease. Instead, its Discussion cites a standardized melanoma event ratio of 3.3 in one group of patients with Parkinson’s disease. (LLM, conf=0.90)
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Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup>
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- Authors
- Gao, X., Simon, K. C., Han, J., Schwarzschild, M. A., & Ascherio, A.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Gao, Xiang
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2009-01
- Volume
- 65
- Issue
- 1
- Pages
- 76-82
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2639631
- OpenAlex
- W1989227641
- Cited by
- 116
- References
- 52
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 12 · 2015: 5 · 2014: 5 · 2013: 8 · 2012: 7
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS048517)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Parkinson's disease, hair color, pigmentation, MC1R, melanoma risk, genetic susceptibility, red hair
- MeSH terms
- Adolescent, Age Factors, Arginine, Cysteine, Female, Follow-Up Studies, Genotype, Hair Color, Humans, Male, Parkinson Disease, Polymorphism, Genetic, Retrospective Studies, Risk Factors, Sensitivity and Specificity, Case-Control Studies, Risk Assessment, Genetic Determinism, Receptor, Melanocortin, Type 1, Young Adult
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