Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children

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Utge , S , Räikkönen , K , Kajantie , E , Lipsanen , J , Andersson , S , Strandberg , T , Reynolds , R M , Eriksson , J G & Lahti , J 2018 , ' Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children ' , Psychoneuroendocrinology , vol. 93 , pp. 1-7 . https://doi.org/10.1016/j.psyneuen.2018.04.009

Title: Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children
Author: Utge, Siddheshwar; Räikkönen, Katri; Kajantie, Eero; Lipsanen, Jari; Andersson, Sture; Strandberg, Timo; Reynolds, Rebecca M.; Eriksson, Johan G.; Lahti, Jari
Contributor organization: Medicum
Department of Psychology and Logopedics
Lastentautien yksikkö
Children's Hospital
Clinicum
HUS Children and Adolescents
Timo Strandberg / Principal Investigator
Department of Medicine
Geriatrian yksikkö
HUS Internal Medicine and Rehabilitation
Johan Eriksson / Principal Investigator
Department of General Practice and Primary Health Care
Helsinki University Hospital Area
Helsinki Collegium for Advanced Studies
Developmental Psychology Research Group
Teachers' Academy
Date: 2018-07
Language: eng
Number of pages: 7
Belongs to series: Psychoneuroendocrinology
ISSN: 0306-4530
DOI: https://doi.org/10.1016/j.psyneuen.2018.04.009
URI: http://hdl.handle.net/10138/300875
Abstract: Purpose: Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood. Variation in genes SERPINA6 encoding for CBG, SERPINA2 and SERPINAI (serpin family A member 6, 2, and 1) have been shown to influence morning plasma cortisol and CBG in adults. However, association of this genetic variation with diurnal and stress-induced salivary cortisol remain unknown. This study aims to investigate the effect of genetic variation in SERPINA6/2/1 loci on diurnal and stress-induced salivary cortisol in children. Methods: We studied 186, 8-year-old children with genome-wide genotyping. We generated weighted polygenic risk score (PRS) based on 6 genome-wide significant SNPs (rs11621961, rs11629171, rs7161521, rs2749527, rs3762132, rs4900229) derived from the CORNET meta-analyses. Salivary cortisol was measured across one day and in response to the Trier Social Stress Test for Children (TSST-C). Results: Mixed models, adjusted for covariates, showed that the PRS x sampling time interactions associated with diurnal (P <0.001) and stress-induced (P = 0.009) salivary cortisol. In the high PRS group (dichotomized at median) the diurnal salivary cortisol pattern decreased less from awakening to bedtime than in the low PRS group (standardized estimates of sampling time -0.64 vs. -0.73, P <0.0001 for both estimates). In response to stress, salivary cortisol increased in the high PRS group while it remained unchanged in the low PRS group (standardized estimates of sampling time 0.12, P = 0.015 vs. -0.06, P = 0.16). These results were mainly driven by minor alleles of rs7161521 (SERPINA6) and rs4900229 (SERPINAI). Conclusions: Genetic variation in SERPINA6/2/1loci may underpin higher hypothalamic-pituitary-adrenocortical axis activity in children.
Subject: Polygenic risk score (PRS)
SERPINA6
SERPINA2
SERPINA1
Salivary cortisol
Stress
CORTICOSTEROID-BINDING GLOBULIN
LICORICE CONSUMPTION
PSYCHOSOCIAL STRESS
CORTISOL RESPONSE
SALIVARY CORTISOL
GENE
HORMONE
FATIGUE
GLUCOCORTICOIDS
POLYMORPHISMS
515 Psychology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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