Advancing ability to predict who is likely to develop depression holds great potential in reducing the disease burden. Here, we use the predictable and large increase in depression with physician training stress to identify predictors of depression. Applying the major depressive disorder polygenic risk score (MDD-PRS) derived from the most recent Psychiatric Genomics Consortium-UK Biobank-23andMe genome-wide association study to 5,227 training physicians, we found that MDD-PRS predicted depression under training stress (β = 0.095, P = 4.7 × 10-16) and that MDD-PRS was more strongly associated with depression under stress than at baseline (MDD-PRS × stress interaction β = 0.036, P = 0.005). Further, known risk factors accounted for substantially less of the association between MDD-PRS and depression when under stress than at baseline, suggesting that MDD-PRS adds unique predictive power in depression prediction. Finally, we found that low MDD-PRS may have particular use in identifying individuals with high resilience. Together, these findings suggest that MDD-PRS holds promise in furthering our ability to predict vulnerability and resilience under stress.

中文翻译：

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压力下抑郁风险和复原力的基因组预测。

预测谁可能患上抑郁症的先进能力在减轻疾病负担方面具有巨大潜力。在这里，我们使用医生训练压力下抑郁症的可预测且大幅增加来确定抑郁症的预测因素。将来自最近的Psychiatric Genomics Consortium-UK Biobank-23andMe全基因组关联研究的主要抑郁症多基因风险评分（MDD-PRS）应用于5,227名训练医师，我们发现MDD-PRS可以预测训练压力下的抑郁症（β= 0.095，P = 4.7×10-16），并且与压力下的抑郁症相比，MDD-PRS与基线状态下的抑郁相关性更强（MDD-PRS×应力相互作用β= 0.036，P = 0.005）。此外，在压力下，已知的危险因素在MDD-PRS与抑郁症之间的关联中所占的比例要比基线时低得多，提示MDD-PRS在抑郁症预测中增加了独特的预测能力。最后，我们发现低MDD-PRS可能在识别具有高复原力的个人中特别有用。总之，这些发现表明，MDD-PRS在增强我们预测压力下的脆弱性和恢复能力方面具有广阔的前景。