Abstract

Cortisol concentrations in hair are used to create hormone profiles spanning months. This method allows assessment of chronic cortisol exposure, but might be biased by hair pigmentation: dark hair was previously related to higher concentrations. It is unclear whether this association arises from local effects, such as increased hormone extractability, or whether the association represents systemic differences arising from population stratification. We tested the hypothesis that hair pigmentation gene variants are associated with varying cortisol levels independent of genetic ancestry. Hormone concentrations and genotype were measured in 1674 children from the Generation R cohort at age 6. We computed a polygenic score of hair color based on 9 single nucleotide polymorphisms. This score was used to predict hair cortisol concentrations, adjusted for genetic ancestry, sex, age and corticosteroid use. A 1-standard deviation (SD) higher polygenic score (darker hair) was associated with 0.08 SD higher cortisol levels (SE = 0.03, p = 0.002). This suggests that variation in hair cortisol concentrations is partly explained by local hair effects. In multi-ancestry studies this hair pigmentation bias can reduce power and confound results. Researchers should therefore consider adjusting analyses by reported hair color, by polygenic scores, or by both.

Highlights

  • Cortisol concentrations in hair are used to create hormone profiles spanning months

  • To explore the nature of the hair color and hair cortisol association, we investigated whether single nucleotide polymorphisms (SNPs) associated with hair pigmentation are associated with hair cortisol levels in childhood independent of genetic ancestry

  • The polygenic score of hair color was significantly associated with hair cortisol and cortisone levels after strict adjustment for genetic ancestry

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Summary

Introduction

Cortisol concentrations in hair are used to create hormone profiles spanning months This method allows assessment of chronic cortisol exposure, but might be biased by hair pigmentation: dark hair was previously related to higher concentrations. It is unclear whether this association arises from local effects, such as increased hormone extractability, or whether the association represents systemic differences arising from population stratification. To explore the nature of the hair color and hair cortisol association, we investigated whether single nucleotide polymorphisms (SNPs) associated with hair pigmentation are associated with hair cortisol levels in childhood independent of genetic ancestry For this purpose we selected 16 SNPs from 10 genes included in the HIrisPlex system previously developed to predict hair and eye color from DNA6, 7.

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