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

doi:10.1210/clinem/dgz016

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 Journal › Article › Academic › peer-review

Abstract

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 language	English
Article number	dgz016
Pages (from-to)	1-10
Number of pages	10
Journal	The Journal of clinical endocrinology and metabolism
Volume	105
Issue number	2
Early online date	14 Oct 2019
DOIs	https://doi.org/10.1210/clinem/dgz016
Publication status	Published - Feb 2020

Bibliographical note

Funding

Financial Support: RA and BRW were supported by a British Heart Foundation Programme Grant and by a Wellcome Trust equipment grant. This work was supported by the Netherlands Organization for Scientific Research (NWO, 51.02.060, 668.772; NWO-MagW 480-04-004; NWO/ SPI 56-464-14192). DIB acknowledges KNAW Academy Professor Award (PAH/6635).

Funders	Funder number
Netherlands Organization for Scientific Research	NWO-MagW 480-04-004, NWO/ SPI 56-464-14192, 51.02.060, 668.772
Wellcome Trust
British Heart Foundation

Cohort Studies

Netherlands Twin Register (NTR)

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title = "Heritability of cortisol production and metabolism throughout adolescence: a twin study",

abstract = "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.",

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

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AU - van Keulen, Britt J

AU - Dolan, Conor V

AU - Andrew, Ruth

AU - Walker, Brian R

AU - Hulshoff Pol, Hilleke E

AU - Boomsma, Dorret I

AU - Rotteveel, Joost

AU - Finken, Martijn J J

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Funding

Cohort Studies

Access to Document

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