Genetic influences on hormonal markers of chronic hypothalamic–pituitary–adrenal function in human hair

Abstract

Background Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary, and serum measures are influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. Methods In a socioeconomically diverse sample of 1,070 twins/multiples (ages 7.80–19.47 years), we estimated effects of sex, age, and socioeconomic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. Results Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. Conclusions Genetic factors account for sizable proportions of gluccocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age, and genotype than to experiential factors that cluster within nuclear families.

Emotion regulation moderates the association between parent and child hair cortisol concentrations

“…Twin studies have demonstrated the heritability of basal salivary cortisol (Bartels, Geus, Kirschbaum, Sluyter, & Boomsma, 2003;Ouellet-Morin et al, 2008) and animal studies have indicated the heritability of HCC in monkeys (Fairbanks et al, 2011). Recently, the first genetic study examining the role of genetic variation of long-term cortisol exposure revealed that genetic factors accounted for about half the variation in HCC (Tucker-Drob et al, 2017). Thus, the relation of parent and child HCC may be due, in part, to shared genetic alleles.…”

Predicting hair cortisol levels with hair pigmentation genes: a possible hair pigmentation bias

“…Second, the hair cortisol differences might reflect genetic differences in subpopulations (population stratification). For example, since hair color is strongly linked to genetic ancestry, it might be a marker of genetic variations related to cortisol metabolism or sensitivity 3 . Third, color might be a marker for minority status and the related stress, which would explain higher systemic cortisol levels 1 , 2 , 4 .…”

Hair cortisol and inhaled corticosteroid use in asthmatic children

“…Also, genes associated with an increased risk of adrenal suppression in children using glucocorticosteroids have been localized. 6,32 Genotyping might further clarify the relation between corticosteroids and adrenal function. However adrenal function tests will still be needed when suspecting a case of adrenal insufficiency.…”