Chen Tzu-Ting, Chen Chia-Yen, Liu Chao-Yu, Lee Jiwoo, Ganna Andrea, Feng Yen-Chen Anne, Lin Yen-Feng
Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
Biogen, Cambridge, MA, USA.
Mol Psychiatry. 2025 Feb 20. doi: 10.1038/s41380-025-02928-y.
Childhood maltreatment is increasingly recognized as a pivotal risk factor for adverse health outcomes. However, comprehensive analyses of its long-term impact are scarce. This study aims to fill this gap by examining the genetic architectures of childhood maltreatment and its influence on adult health and socioeconomic outcomes. Utilizing data from the UK Biobank (N = 129,017), we conducted sex-combined and sex-stratified genome-wide association studies to identify genomic loci associated with five childhood maltreatment subtypes. We then performed genetic correlation and Mendelian randomization (MR) analyses to assess the effects of childhood maltreatment on high-burden diseases, healthcare costs, lifespan, and educational attainment. We identified several novel loci for childhood maltreatment, including one locus for sexual abuse in sex-combined analysis, one novel locus for sexual abuse in males, one locus for emotional neglect in females, and one locus for sexual abuse in females. The pairwise genetic correlations between subtypes of childhood maltreatment were moderate to high, and similar patterns of genetic correlations between childhood maltreatment subtypes were observed in males and females. Childhood maltreatment was genetically correlated with ten out of 16 high-burden diseases significantly after multiple testing correction. Moreover, MR analyses suggest childhood maltreatment may increase the risk of age-related and other hearing loss, low back pain, major depressive disorder, and migraine in adulthood, and reduce the lifespan. Our study elucidates the genetic architecture of specific childhood maltreatment subtypes and the influence of childhood maltreatment on health outcomes in adulthood, highlighting the enduring influence of childhood maltreatment on lifelong health consequences. It is important to develop prevention strategies to lower the incidence of childhood maltreatment and provide support and care for victims of childhood maltreatment for better long-term health outcomes in the population.
童年期受虐日益被视为不良健康后果的关键风险因素。然而，对其长期影响的全面分析却很匮乏。本研究旨在通过考察童年期受虐的遗传结构及其对成人健康和社会经济结局的影响来填补这一空白。利用英国生物银行（样本量N = 129,017）的数据，我们进行了性别合并及按性别分层的全基因组关联研究，以识别与五种童年期受虐亚型相关的基因组位点。然后，我们进行了遗传相关性分析和孟德尔随机化（MR）分析，以评估童年期受虐对高负担疾病、医疗费用、寿命和教育程度的影响。我们识别出了几个童年期受虐的新位点，包括性别合并分析中的一个性虐待位点、男性中的一个性虐待新位点、女性中的一个情感忽视位点以及女性中的一个性虐待位点。童年期受虐各亚型之间的成对遗传相关性为中度至高，且在男性和女性中观察到童年期受虐亚型之间的遗传相关性模式相似。在进行多重检验校正后，童年期受虐与16种高负担疾病中的10种存在显著的遗传相关性。此外，MR分析表明，童年期受虐可能会增加成年后患与年龄相关的及其他听力损失、腰痛、重度抑郁症和偏头痛的风险，并缩短寿命。我们的研究阐明了特定童年期受虐亚型的遗传结构以及童年期受虐对成年期健康结局的影响，凸显了童年期受虐对终身健康后果的持久影响。制定预防策略以降低童年期受虐的发生率，并为童年期受虐受害者提供支持和护理，对于改善人群的长期健康结局非常重要。
