TY  - JOUR
AU  - Herrera-Rivero, Marisol
AU  - Garvert, Linda
AU  - Horn, Katrin
AU  - Löbner, Margrit
AU  - Weitzel, Elena Caroline
AU  - Stoll, Monika
AU  - Lichtner, Peter
AU  - Teismann, Henning
AU  - Teumer, Alexander
AU  - Van der Auwera, Sandra
AU  - Völzke, Henry
AU  - Völker, Uwe
AU  - Andlauer, Till F. M.
AU  - Meinert, Susanne
AU  - Heilmann-Heimbach, Stefanie
AU  - Forstner, Andreas J.
AU  - Streit, Fabian
AU  - Witt, Stephanie H.
AU  - Kircher, Tilo
AU  - Dannlowski, Udo
AU  - Scholz, Markus
AU  - Riedel-Heller, Steffi G.
AU  - Grabe, Hans J.
AU  - Baune, Bernhard T.
AU  - Berger, Klaus
TI  - A meta-analysis of genome-wide studies of resilience in the German population
JO  - Molecular psychiatry
VL  - 30
IS  - 2
SN  - 1359-4184
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00219
SP  - 497 - 505
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Genome-Wide Association Study: methods
KW  - Resilience, Psychological
KW  - Germany
KW  - Multifactorial Inheritance: genetics
KW  - Male
KW  - Female
KW  - Polymorphism, Single Nucleotide: genetics
KW  - Personality: genetics
KW  - Mental Health
KW  - Adult
KW  - Cohort Studies
KW  - Middle Aged
LB  - PUB:(DE-HGF)16
C6  - pmid:39112778
C2  - pmc:PMC11746137
DO  - DOI:10.1038/s41380-024-02688-1
UR  - https://pub.dzne.de/record/276147
ER  -