The Genetic Basis of Resilience: A Genome-Wide Association Study Meta-Analysis in the German Population

Abstract

Abstract 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). Our analyses suggested five genomic loci (p < 1x10− 5) in the variant-based analysis and 33 potential candidates (p < 1x10− 4) in the gene-based analysis, including three genome-wide significant genes (ROBO1, CIB3 and LYPD4), associated with resilience. 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. These observations improve our understanding of the genetic architecture underlying resilience and of its relationship with other personality traits and mental health.