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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