Ter Kuile Abigail R, Hübel Christopher, Cheesman Rosa, Coleman Jonathan R I, Peel Alicia J, Levey Daniel F, Stein Murray B, Gelernter Joel, Rayner Christopher, Eley Thalia C, Breen Gerome
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
National Institute for Health and Care Research Maudsley Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
Biol Psychiatry Glob Open Sci. 2023 Mar 24;3(4):716-724. doi: 10.1016/j.bpsgos.2023.03.003. eCollection 2023 Oct.
Decades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.
We used genome-wide association study summary statistics of childhood maltreatment, defined as reporting of abuse (emotional, sexual, and physical) and neglect (emotional and physical) ( = 185,414 participants). We calculated genetic correlations () between reported childhood maltreatment and 576 traits to identify phenotypes that might explain the heritability of reported childhood maltreatment, retaining those with || > 0.25. We specified multiple regression models using genomic structural equation modeling to detect residual genetic variance in childhood maltreatment after accounting for genetically correlated traits.
In 2 separate models, the shared genetic component of 12 health and behavioral traits and 7 psychiatric disorders accounted for 59% and 56% of heritability due to common genetic variants (single nucleotide polymorphism-based heritability [h]) of childhood maltreatment, respectively. Genetic influences on h of childhood maltreatment were generally accounted for by a shared genetic component across traits. The exceptions to this were general risk tolerance, subjective well-being, posttraumatic stress disorder, and autism spectrum disorder, identified as independent contributors to h of childhood maltreatment. These 4 traits alone were sufficient to explain 58% of h of childhood maltreatment.
We identified putative traits that reflect h of childhood maltreatment. Elucidating the mechanisms underlying these associations may improve trauma prevention and posttraumatic intervention strategies.
数十年的研究表明,包括创伤自我报告在内的环境暴露具有部分遗传性。可遗传特征可能会影响对环境因素的暴露和解读。识别与自我报告创伤相关的遗传因素有助于我们更好地理解暴露的易感性以及对生活事件的解读。
我们使用了儿童期虐待的全基因组关联研究汇总统计数据,儿童期虐待定义为报告遭受虐待(情感、性和身体方面)以及忽视(情感和身体方面)(n = 185,414名参与者)。我们计算了报告的儿童期虐待与576个性状之间的遗传相关性(rg),以识别可能解释报告的儿童期虐待遗传性的表型,保留|rg| > 0.25的表型。我们使用基因组结构方程模型指定多元回归模型,以在考虑遗传相关性状后检测儿童期虐待中的残余遗传方差。
在2个独立模型中,12种健康和行为性状以及7种精神疾病的共享遗传成分分别占儿童期虐待常见遗传变异(基于单核苷酸多态性的遗传力[h2])所致遗传力的59%和56%。对儿童期虐待h2的遗传影响通常由各性状间的共享遗传成分所解释。例外情况是一般风险耐受性、主观幸福感、创伤后应激障碍和自闭症谱系障碍,它们被确定为儿童期虐待h2的独立贡献因素。仅这4个性状就足以解释儿童期虐待h2的58%。
我们识别出了反映儿童期虐待遗传力的推定性状。阐明这些关联背后的机制可能会改善创伤预防和创伤后干预策略。