Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa.
Transl Psychiatry. 2021 Jul 2;11(1):358. doi: 10.1038/s41398-021-01434-3.
Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how in utero exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study-the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (β = -1.95; p = 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.
与实际年龄相比,加速的表观遗传衰老已被发现与成年人的死亡率风险增加相关。然而,对于宫内暴露是否以及如何塑造儿童出生时的妊娠期表观遗传年龄(EA),人们知之甚少。我们旨在探索南非出生队列研究——Drakenstein 儿童健康研究中,母亲的心理社会危险因素与儿童出生时的妊娠期 EA 偏差(即相对于实际年龄,EA 较高或较低)之间的关联。母亲的心理社会危险因素包括创伤/压力源暴露;创伤后应激障碍(PTSD);抑郁;心理困扰;以及酒精/烟草使用。使用先前为新生儿设计的表观遗传时钟计算儿童出生时的妊娠期 EA;并将 EA 偏差计算为 EA 与实际妊娠年龄之间线性模型的残差。然后使用双变量线性回归模型探索母亲/儿童危险因素与儿童出生时的 EA 残差之间的未调整关联。之后,使用多变量回归方法确定调整后的关联。目前的分析包括 271 对母婴对子的数据。在多变量回归模型中,母亲的 PTSD 与儿童出生时的妊娠期 EA 残差呈显著负相关(β=-1.95;p=0.018),控制了研究地点、儿童的性别、出生时的头围、出生体重、分娩方式、母亲估计的家庭收入、入学时的 BMI、HIV 状态、贫血、心理困扰和产前吸烟或饮酒。鉴于这一初步发现的新颖性及其潜在的转化意义,进一步研究阐明潜在的生物学途径并探索 EA 偏差的临床意义是必要的。