Polygenic risk score of SERPINA6/SERPINA1 associates with diurnal and stress-induced HPA axis activity in children

PSYCHONEUROENDOCRINOLOGY

卷:93

Article

Utge, Siddheshwar^1,2  Raikkonen, Katri¹  Kajantie, Eero^3,4,5,6,7  Lipsanen, Jari¹  Andersson, Sture^4,5  Strandberg, Timo^8,9  Reynolds, Rebecca M.¹⁰  Eriksson, Johan G.^2,3,5,11  Lahti, Jari^1,2,12 

[1] Univ Helsinki, Fac Med, Dept Psychol & Logoped, Haartmaninkatu 3, FIN-00014 Helsinki, Finland

[2] Folkhalsan Res Ctr, Helsinki, Finland

[3] Natl Inst Hlth & Welf, Helsinki, Finland

[4] Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland

[5] Univ Helsinki, Helsinki, Finland

[6] Oulu Univ Hosp, MRC Oulu, PEDEGO Res Unit, Oulu, Finland

[7] Univ Oulu, Oulu, Finland

[8] Univ Helsinki, Cent Hosp, Geriatr, Helsinki, Finland

[9] Univ Oulu, Inst Hlth Sci Geriatr, Oulu, Finland

[10] Univ Edinburgh, BHF Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland

[11] Helsinki Univ Hosp, Unit Gen Practice & Primary Hlth Care, Helsinki, Finland

[12] Univ Helsinki, Helsinki Collegium Adv Studies, Helsinki, Finland

关键词: Polygenic risk score (PRS);    SERPINA6;    SERPINA2;    SERPINA1;    Salivary cortisol;    Stress;   

DOI  :  10.1016/j.psyneuen.2018.04.009

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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