Hypothalamic-pituitary-adrenal Axis Multilocus Genetic Variation, Childhood Parenting and Adolescent Anxiety Symptoms: Evidence of Cumulative Polygenic Plasticity.

Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 0333507 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-6601 (Electronic) Linking ISSN: 00472891 NLM ISO Abbreviation: J Youth Adolesc Subsets: MEDLINE

Publication: 1999- : New York, NY : Kluwer Academic/Plenum Publishers
Original Publication: New York, Plenum Press.

Anxiety*/genetics ; Hypothalamo-Hypophyseal System*/physiology ; Parenting* ; Pituitary-Adrenal System*/physiology; Adolescent ; Female ; Genetic Variation ; Humans ; Hydrocortisone ; Male ; Multifactorial Inheritance ; Stress, Psychological/genetics ; Young Adult

Research suggests that genetic variants that regulate the hypothalamic-pituitary-adrenal (HPA) axis function moderate the association between parenting and anxiety symptoms, but these studies have primarily focused on (i) individual genes with very small and unreliable effect and (ii) the role of mothers as opposed to fathers. Using a multilocus genetic profile score approach, the current study is the first to examine the moderation effect of HPA-axis multilocus genetic variants on the associations of both maternal and paternal parenting with adolescent anxiety symptoms. In a sample of Chinese Han adolescents (N = 772; 50.1% girls; M age  = 16.48 ± 1.40 years, range: 15-20 years), a theory-driven multilocus genetic profile score was computed by counting the numbers of alleles that were previously linked to heightened stress reactivity in six HPA-axis related genes. This HPA-axis related multilocus genetic profile score equivalently interacted with both maternal and paternal parenting in the prediction of adolescent anxiety symptoms. Consistent with cumulative polygenic plasticity hypothesis of differential susceptibility model, adolescents with more versus low alleles linked to heightened stress reactivity not only suffered more from poor maternal or paternal parenting quality, but also benefited more from high maternal or paternal parenting quality. However, none of the individual HPA-axis genes within this multilocus genetic profile score yielded a significant gene-by-environment (G × E) interaction when examined in isolation. The findings survived after internal replication analysis and a novel, valid influence statistic DFBETAS analysis, demonstrating the robustness of the results. The current study highlights the potential value of using a multilocus approach to understand G × E effects underlying anxiety symptoms and emphasizes the role of both mothers and fathers in such gene-parenting interactions, especially in Chinese families.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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31800936 National Natural Science Foundation of China; ZR2019BC111 Natural Science Foundation of Shandong Province; 18DJYJ01 Social Science Planning Fund of Shandong Province

Keywords: Anxiety symptoms; Gene-environment interaction; Hypothalamic-pituitary-adrenal axis; Influence statistic; Multilocus genetic profile score; Paternal parenting

WI4X0X7BPJ (Hydrocortisone)

Date Created: 20220427 Date Completed: 20220628 Latest Revision: 20220629

20231215

10.1007/s10964-022-01610-8

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