Heritability of cortisol production and metabolism throughout adolescence: a twin study

Britt J van Keulen, Conor V Dolan, Ruth Andrew, Brian R Walker, Hilleke E Hulshoff Pol, Dorret I Boomsma, Joost Rotteveel, Martijn J J Finken

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)


CONTEXT: Inter-individual differences in cortisol production and metabolism emerge with age, and may be explained by genetic factors.

OBJECTIVE: To estimate the relative contributions of genetic and environmental factors to inter-individual differences in cortisol production and metabolism throughout adolescence.

DESIGN: Prospective follow-up study of twins.

SETTING: Nationwide register.

PARTICIPANTS: 218 mono- and dizygotic twins (N=109 pairs) born between 1995-1996, recruited from the Netherlands Twin Register. Cortisol metabolites were determined in 213, 169 and 160 urine samples at the ages of 9, 12 and 17y, respectively.

MAIN OUTCOME MEASURES: The total contribution of genetic factors (broad-sense heritability), and shared and unshared environmental influences to inter-individual differences in cortisol production, and activities of 5α-reductase, 5β-reductase, 11β-hydroxysteroid dehydrogenases and cytochrome P450 3A4.

RESULTS: For cortisol production rate at the ages of 9, 12 and 17y, broad-sense heritability was estimated as: 42%, 30% and 0%, respectively and the remainder of the variance was explained by unshared environmental factors. For cortisol metabolism indices, the following heritability was observed: for the A-ring reductases (5α-and 5β-reductases), broad-sense heritability increased with age (to>50%), while for the other indices (renal 11β-HSD2, global 11β-HSD and CYP3A4), the contribution of genetic factors was highest (68%, 18% and 67%, respectively) at age 12y.

CONCLUSIONS: The contribution of genetic factors to inter-individual differences in cortisol production decreased between 12 and 17y, indicative of a predominant role of individual circumstances. For cortisol metabolism, distinct patterns of genetic and environmental influences were observed, with heritability that either increased with age or peaked at age 12y.

Original languageEnglish
Article numberdgz016
Pages (from-to)1-10
Number of pages10
JournalThe Journal of clinical endocrinology and metabolism
Issue number2
Early online date14 Oct 2019
Publication statusPublished - Feb 2020

Cite this