Genetic architectures of childhood maltreatment and causal influence of childhood maltreatment on health outcomes in adulthood

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.