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

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

doi:10.1038/s41598-017-11852-3

Abstract

Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.

Highlights

Research has generated robust evidence that chronic stress is a risk factor for mental disorders[1,2]
Perceived stress, depressive symptoms and neuroticism showed an association with age, and perceived stress and neuroticism showed an interaction of sex and age
Regarding the phenotypic and genetic correlations of hair cortisol concentration (HCC) with psychological variables, the present analyses demonstrated that shared genetic factors underlie the association between the psychological variables perceived stress, depressive symptoms, and neuroticism

Summary

Introduction

Research has generated robust evidence that chronic stress is a risk factor for mental disorders[1,2]. Studies investigating the relationship of HCC with cortisol levels in other tissues show the highest correlations (up to r = 0.61) with cumulative or average cortisol measures acquired over several days or weeks[14,15,16,17] While these studies which assessed multiple measurement-points have been mainly carried out using saliva and urine, studies which used serum and plasma blood samples, have been mainly based on single assessments, and the observed correlations were lower or non-significant (e.g. refs[18,19,20]). While stressful environmental factors play a major role in HPA axis activation, twin studies have indicated that genetic factors have a substantial impact on the secretion of cortisol, especially morning cortisol. The authors found no phenotypic or genotypic association between cortisol levels and neuroticism

Methods

Discussion

Conclusion