POLYGENIC RISK SCORES FOR A SPECTRUM OF PSYCHIATRIC OUTCOMES ARE ALSO ASSOCIATED WITH DEPRESSION TRAJECTORIES FROM CHILDHOOD TO EARLY ADULTHOOD: FINDINGS FROM THE AVON LONGITUDINAL STUDY OF PARENTS AND CHILDREN

IF 6.1 2区 医学 Q1 CLINICAL NEUROLOGY
Ruby Tsang, Nicholas Timpson
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引用次数: 0

Abstract

Depression is a complex and multifactorial disorder that has genetic and environmental influences. Genome-wide association studies have shown that common genetic variants are implicated in depression. These common variants, when combined into polygenic risk scores, are associated with depression case status, severity and age of onset. However, less is known about how genetic risk affects change in depression symptoms longitudinally. Furthermore, psychiatric disorders are comorbid and recent studies have shown genetic risk is shared between them, but the association between this shared polygenic risk and how depression manifests and changes over time is not yet understood.
We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Self-reported depressive symptoms were assessed on 10 occasions between the ages of 10 and 25 using the 13-item Short Mood and Feelings Questionnaire. Polygenic risk scores (PRS) for major depressive disorder (MDD), anxiety (ANX), neuroticism (NEU), and schizophrenia (SCZ) were computed with PRSice-2 using summary statistics from recent genome-wide associations studies, in which ALSPAC was not included. Additionally, we used genomic structural equation modelling (GSEM) to create a multi-trait PRS of MDD, ANX, NEU, SCZ, bipolar disorder, autism spectrum disorder, and attention deficit hyperactivity disorder, to capture the spectrum of psychopathology and explored how this genetic risk score was associated with depression trajectories.
We modelled depression trajectories using generalised additive models, with age as the time metric, and included sex, age-sex interaction, PRS, age-PRS interaction, and the first 10 principal components as predictors. We ran separate models for each PRS.
Depression trajectories for those in the top and bottom deciles of MDD and NEU PRS start to show divergence around mid- to late-adolescence with higher genetic risk associated with worse trajectories. With the multi-trait PRS, differences emerge as early as childhood, again with higher genetic risk indicative of worse trajectories. In these three models, the separation between the trajectories then continues to increase into adulthood. No clear pattern of separation was observed with the ANX or SCZ PRS.
These findings suggest that psychiatric PRS are associate with (and may influence) the longitudinal course of depressive symptoms from childhood into early adulthood. The multi-trait PRS was superior to PRS of individual psychiatricdisorders in delineating depression trajectories in association with genetic risk. One interpretation is that a spectrum of psychiatric genetic risk could underpin developmental differences in depression trajectories.
一系列精神疾病结果的多基因风险评分也与从童年到成年早期的抑郁轨迹有关:阿文父母与子女纵向研究的结果
抑郁症是一种复杂的多因素疾病,受遗传和环境影响。全基因组关联研究表明,常见的基因变异与抑郁症有关。这些常见变异组合成多基因风险评分后,与抑郁症的病例状态、严重程度和发病年龄有关。然而,人们对遗传风险如何影响抑郁症状的纵向变化知之甚少。此外,精神疾病具有并发性,最近的研究表明,它们之间存在共同的遗传风险,但这种共同的多基因风险与抑郁症的表现形式和随时间变化之间的关联尚不清楚。我们使用了雅芳父母与子女纵向研究(ALSPAC)的数据,在 10 至 25 岁期间,使用 13 项短期情绪和感觉问卷对自我报告的抑郁症状进行了 10 次评估。重度抑郁症(MDD)、焦虑症(ANX)、神经质(NEU)和精神分裂症(SCZ)的多基因风险评分(PRS)是通过 PRSice-2 计算得出的,计算时使用了近期全基因组关联研究(ALSPAC 未包括在内)的汇总统计数据。此外,我们还使用基因组结构方程建模(GSEM)创建了一个包含 MDD、ANX、NEU、SCZ、双相情感障碍、自闭症谱系障碍和注意缺陷多动障碍的多性状 PRS,以捕捉精神病理学的谱系,并探讨了这一遗传风险评分与抑郁轨迹的关联。我们使用广义加法模型对抑郁轨迹进行建模,以年龄作为时间度量,并将性别、年龄-性别交互作用、PRS、年龄-PRS 交互作用和前 10 个主成分作为预测因子。在青春期中后期,MDD 和 NEU PRS 顶部和底部十分位组的抑郁轨迹开始出现分化,遗传风险越高,轨迹越差。在多特质 PRS 中,差异最早出现在儿童时期,同样,遗传风险越高,轨迹越差。在这三种模型中,轨迹之间的差异会持续到成年期。这些研究结果表明,精神病学 PRS 与抑郁症状从童年到成年早期的纵向发展过程有关(并可能对其产生影响)。多特质PRS在描述与遗传风险相关的抑郁轨迹方面优于单个精神障碍的PRS。一种解释是,一系列精神病遗传风险可能是抑郁症发展轨迹差异的基础。
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来源期刊
European Neuropsychopharmacology
European Neuropsychopharmacology 医学-精神病学
CiteScore
10.30
自引率
5.40%
发文量
730
审稿时长
41 days
期刊介绍: European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.
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