Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience. We performed variant- and gene-based meta-analyses of genome-wide association studies from six German cohorts (N = 15822) using the 11-item version of the Resilience Scale (RS-11) as outcome measure. Variant- and gene-level results were combined to explore the biological context using network analysis. In addition, we conducted tests of correlation between RS-11 and the polygenic scores (PGSs) for 12 personality and mental health traits in one of these cohorts (PROCAM-2, N = 3879). The variant-based analysis found no signals associated with resilience at the genome-wide level (p < 5 × 10⁻⁸), but suggested five genomic loci (p < 1 × 10⁻⁵). The gene-based analysis identified three genes (ROBO1, CIB3 and LYPD4) associated with resilience at genome-wide level (p < 2.48 × 10⁻⁶) and 32 potential candidates (p < 1 × 10⁻⁴). Network analysis revealed enrichment of biological pathways related to neuronal proliferation and differentiation, synaptic organization, immune responses and vascular homeostasis. We also found significant correlations (FDR < 0.05) between RS-11 and the PGSs for neuroticism and general happiness. Overall, our observations suggest low heritability of resilience. Large, international efforts will be required to uncover the genetic factors that contribute to shape trait resilience. Nevertheless, as the largest investigation of the genetics of resilience in general population to date, our study already offers valuable insights into the biology potentially underlying resilience and resilience’s relationship with other personality traits and mental health.

韧性是适应压力生活事件的能力。因此，这种特征与身体和心理功能和状况有关。在这里，我们的目的是确定有助于塑造弹性的遗传因素。我们使用弹性量表 (RS-11) 的 11 项版本作为结果测量，对来自 6 个德国队列 (N = 15822) 的全基因组关联研究进行了基于变异和基因的荟萃分析。将变异和基因水平的结果结合起来，利用网络分析来探索生物学背景。此外，我们还对其中一个队列（PROCAM-2，N = 3879）中 12 种人格和心理健康特征的 RS-11 与多基因评分 (PGS) 之间的相关性进行了测试。基于变体的分析没有发现与全基因组水平的恢复力相关的信号（p < 5 × 10 ^-8 ），但提出了五个基因组位点（p < 1 × 10 ^-5 ）。基于基因的分析确定了与全基因组水平恢复力相关的三个基因（ ROBO1 、 CIB3和LYPD4 ）（p < 2.48 × 10 ^-6 ）和 32 个潜在候选基因（p < 1 × 10 ^-4 ）。网络分析揭示了与神经元增殖和分化、突触组织、免疫反应和血管稳态相关的生物途径的丰富。我们还发现 RS-11 与神经质和总体幸福感的 PGS 之间存在显着相关性 (FDR < 0.05)。总体而言，我们的观察表明复原力遗传力较低。需要大量的国际努力来揭示有助于塑造特质恢复力的遗传因素。 尽管如此，作为迄今为止对普通人群复原力遗传学最大规模的调查，我们的研究已经为复原力潜在的生物学以及复原力与其他人格特质和心理健康的关系提供了有价值的见解。