Disordered eating and self-harm commonly co-occur in young people suggesting potential for shared underlying causes. Body image dissatisfaction (BID) has been recognised as a psychological correlate of body size, associated with both disordered eating and self-harm. However, the investigation into etiological pathways early in the lifecourse to provide detail on how body size and BID may foster disordered eating and self-harm remains largely unexplored. Employing data from two large population-based cohorts, the UK Biobank and the Avon Longitudinal Study of Parents And Children (ALSPAC), we conducted bidirectional Mendelian randomization (MR) to determine the causal direction of effect between genetically predicted prepubertal body size and two measures of BID indicating (i) desire to be smaller, and (ii) desire to be larger. We then used multivariable regression followed by counterfactual mediation analyses. Bidirectional MR indicated robust evidence that increased genetically predicted prepubertal body size increased desire to be smaller and decreased desire to be larger. Evidence for the reverse causal direction was negligible. These findings remained very similar across sensitivity analyses. In females and males, multivariable regression analyses demonstrated that being overweight increased the risk of disordered eating (risk ratio (RR), 95% confidence interval (CI): 1.19, 1.01 to 1.40 and 1.98, 1.28 to 3.05, respectively) and self-harm (RR, 95% CI: 1.35, 1.04 to 1.77 and 1.55, 0.86 to 2.81, respectively), while being underweight was protective against disordered eating (RR, 95% CI: 0.57, 0.40 to 0.81 and 0.81, 0.38 to 1.73, respectively). There was weak evidence of an increase in the risk of self-harm among underweight individuals. Mediation analyses indicated that the relationship between being overweight and subsequent disordered eating was largely mediated by the desire to be smaller. Our research carries important public health implications, suggesting distinct risk profiles for self-harm and disordered eating in relation to weight and body image. In addition, a better understanding of genetically predicted prepubertal BID may be valuable in the prevention and treatment of disordered eating and self-harm in adolescence.

饮食失调和自残通常同时发生在年轻人中，这表明潜在的共同根本原因。身体形象不满意（BID）已被认为是与体型相关的心理因素，与饮食失调和自残有关。然而，对生命历程早期病因学途径的调查，以提供有关体型和 BID 如何促进饮食失调和自残的详细信息，在很大程度上仍未得到探索。我们利用来自英国生物银行和雅芳父母与儿童纵向研究 (ALSPAC) 两个大型人群队列的数据，进行了双向孟德尔随机化 (MR)，以确定基因预测的青春期前体型与两项测量之间的因果方向BID 的值表明 (i) 希望变小，以及 (ii) 希望变大。然后，我们使用多变量回归，然后进行反事实中介分析。双向 MR 提供了强有力的证据，表明基因预测的青春期前体型的增加增加了对变小的渴望，并减少了对变大的渴望。反向因果方向的证据可以忽略不计。这些发现在敏感性分析中仍然非常相似。在女性和男性中，多变量回归分析表明，超重会增加饮食失调的风险（风险比 (RR)、95% 置信区间 (CI) 分别为：1.19、1.01 至 1.40 和 1.98、1.28 至 3.05）和自我认知障碍。危害（RR，95% CI：分别为 1.35、1.04 至 1.77 和 1.55、0.86 至 2.81），而体重过轻可以预防饮食失调（RR，95% CI：0.57、0.40 至 0.81 和 0.81、0.38 至 1.73，分别）。有微弱的证据表明体重不足的人自残的风险有所增加。 中介分析表明，超重与随后的饮食失调之间的关系很大程度上是由想要变瘦的愿望介导的。我们的研究具有重要的公共卫生意义，表明与体重和身体形象相关的自残和饮食失调的独特风险状况。此外，更好地了解基因预测的青春期前 BID 对于预防和治疗青春期饮食失调和自残可能很有价值。