Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

Rietschel, Liz; Streit, Fabian; Zhu, Gu; McAloney, Kerrie; Frank, Josef; Couvy‐Duchesne, Baptiste; Witt, Stephanie H.; Binz, Tina M.; McGrath, John J.; Hickie, Ian B.; Hansell, Narelle K.; Wright, Margaret J.; Gillespie, Nathan A.; Forstner, Andreas J.; Schulze, Thomas G.; Wüst, Stefan; Nöthen, Markus M.; Baumgartner, Markus R.; Walker, Brian R.; Crawford, Andrew; Colodro‐Conde, Lucía; Medland, Sarah E.; Martin, Nicholas G.; Rietschel, Marcella

doi:10.1038/s41598-017-11852-3

Cited by 54 publications

(46 citation statements)

References 77 publications

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“…554 subjects from control groups of five independent studies representing the general healthy population of Switzerland and Australia were enrolled in this study. 374 adolescents were included from the "Brisbane Longitudinal Twin Study" [10,11], 101 adults were 12.23). Among the participants 54 % were female.…”

Section: Subjectsmentioning

confidence: 99%

Endogenous cortisol in keratinized matrices: Systematic determination of baseline cortisol levels in hair and the influence of sex, age and hair color

Binz

Rietschel

Streit

et al. 2018

Forensic Science International

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The measurement of hair cortisol is increasingly used to measure long-term cumulative cortisol levels and investigate its role as an important stress mediator. In this study a comparative statistical analysis of five independent studies (all analyzed in our laboratory) was performed to investigate baseline ranges of cortisol values in hair and evaluate potential influences of sex, age and hair color. Cortisol concentrations in hair of 554 subjects were measured and a comparative statistical analysis was performed. The analysis showed that cortisol levels significantly differ depending on age. The toddler group (7 months (0.6 years) to 3 years) showed significantly higher values (median 10pg/mg, p-value<0.0001, d=0.78) than the adolescent group. The adolescent groups showed significantly lower (p-value<0.0001, d=0.58 and p<0.0001, d=0.13) values (median 2.4pg/mg and 2.8pg/mg) than the adult group (median 5.8pg/mg). Furthermore, in the adult group men showed significantly higher cortisol values than women (p-value<0.05, d=0.17). This effect could not be seen in the adolescent group. Black hair showed higher cortisol concentrations than blond hair (p-value<0.0001, d=1.3). In addition, two rounds of interlaboratory comparisons for hair cortisol samples between four laboratories revealed very consistent results. Our results demonstrate that baseline cortisol levels are generally low in hair thus making a standardized and well-elaborated analytical method indispensable for accurate determination. Age-dependent normative baseline cortisol levels (toddlers, adolescents and adults) are highly recommended based on the comparative analysis comprising five independent studies.

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Section: Subjectsmentioning

confidence: 99%

Endogenous cortisol in keratinized matrices: Systematic determination of baseline cortisol levels in hair and the influence of sex, age and hair color

Binz

Rietschel

Streit

et al. 2018

Forensic Science International

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“…In particular, the effect on an individual may result more from the perceived stress than the event itself, and may be dependent on individual differences in stress-sensitivity [13–18]. Studies of 5-HTT and twin studies suggest that stress-sensitivity may, at least in part, be heritable [19–22]. Despite a complex interaction between MDD, neuroticism and stress, multivariate structural equation models have confirmed a genetic effect on perceived stress, overlapping that on MDD or neuroticism, but with a specific genetic component [21].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

et al. 2018

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Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity.

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“…In contrast, a recent study among adolescents demonstrated a higher long-term stability of cortisol production, as assessed by hair cortisol concentration (HCC), namely a two-year's stability of 0.32 [95% CI (0.16, 0.45); Rietschel et al, 2017]. Measurement of HCC is a relatively new method that enables the assessment of cortisol production over a prolonged period (with 1 cm of hair segment representing cortisol production over a period of 1 month).…”

Section: Discussionmentioning

confidence: 97%

Long-Term Stability of Cortisol Production and Metabolism Throughout Adolescence: Longitudinal Twin Study

et al. 2020

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Life-course experiences have been postulated to program hypothalamus–pituitary–adrenal (HPA) axis activity, suggesting that HPA axis activity is, at least partially, stable over time. Yet, there is paucity of data on the long-term stability of cortisol production and metabolism. We performed a prospective follow-up study in twins recruited from a nationwide register to estimate the stability of cortisol production and metabolism over time, and the contribution of genetic and environmental factors to this stability. In total, 218 healthy mono- and dizygotic twins were included. At the ages of 9, 12 and 17 years, morning urine samples were collected for assessment (by gas chromatography-tandem mass spectrometry) of cortisol metabolites, enabling the calculation of cortisol metabolite excretion rate and cortisol metabolism activity. Our results showed a low stability for both cortisol metabolite excretion rate (with correlations <.20) and cortisol metabolism activity indices (with correlations of .25 to .46 between 9 and 12 years, −.02 to .15 between 12 and 17 years and .09 to .28 between 9 and 17 years). Because of the low stability over time, genetic and environmental contributions to this stability were difficult to assess, although it seemed to be mostly determined by genetic factors. The low stability in both cortisol production and metabolism between ages 9 and 17 years reflects the dynamic nature of the HPA axis.

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Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

Cited by 54 publications

References 77 publications

Endogenous cortisol in keratinized matrices: Systematic determination of baseline cortisol levels in hair and the influence of sex, age and hair color

Endogenous cortisol in keratinized matrices: Systematic determination of baseline cortisol levels in hair and the influence of sex, age and hair color

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Long-Term Stability of Cortisol Production and Metabolism Throughout Adolescence: Longitudinal Twin Study

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