TY - JOUR
T1 - Heritability of cortisol production and metabolism throughout adolescence
T2 - a twin study
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
N1 - © Endocrine Society 2019.
PY - 2020/2
Y1 - 2020/2
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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U2 - 10.1210/clinem/dgz016
DO - 10.1210/clinem/dgz016
M3 - Article
C2 - 31608377
SN - 0021-972X
VL - 105
SP - 1
EP - 10
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 2
M1 - dgz016
ER -