Department of Clinical and Social Sciences in Psychology,University of Rochester,Rochester, NY,USA.
Dev Psychopathol. 2019 Oct;31(4):1339-1352. doi: 10.1017/S0954579418000779.
Research suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene-environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis-related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14-17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene-environment interactions individually accounted for 5%-8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene-environmental interactions linked to affective outcomes among adolescents.
研究表明，与下丘脑-垂体-肾上腺（HPA）轴功能相关的遗传变异可以调节环境应激源与抑郁之间的关联，但使用单一多态性来检验基因-环境相互作用会限制研究的效能。本研究采用多基因遗传特征评分（MGPS）方法来衡量与 HPA 轴相关的遗传变异，并在青少年样本（年龄在 14-17 岁之间，N=241；白人亚组 n=192）中，以抑郁症状为结果，考察了与急性应激、慢性应激和儿童逆境（采用情境威胁访谈方法评估）之间的相互作用。使用 HPA 轴基因（CRHR1、NR3C2、NR3C1、FKBP5）内的 10 个单核苷酸多态性计算加性 MGPS。更高的 MGPS 与青少年的抑郁症状直接相关。此外，MGPS 预测了急性和慢性应激与青少年抑郁症状之间更强的关联，并且调节了人际而非非人际儿童逆境的影响。基因-环境相互作用单独解释了 5%-8%的抑郁症状变异。在经过多次测试校正和按种族分层后，所有结果均得以保留。研究结果表明，使用 MGPS 可以为检验与青少年情感结果相关的基因-环境相互作用提供充分的效能。
