TY - JOUR
T1 - A meta-analysis of genome-wide studies of resilience in the German population
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
N1 - Funding Information:
Special thanks to all cohort participants as well as clinical and scientific staff that make possible such data collections. The authors would like to thank the support from the joint project \u201EIndividualisation in Changing Environments\u201C (InChangE) of the universities of M\u00FCnster and Bielefeld, Germany. The project InChangE received funding from the programme \u201CProfilbildung 2020\u201D, an initiative of the Ministry of Culture and Science of the State of Northrhine Westphalia. The sole responsibility for the content of this publication lies with the authors. The BiDirect Study is supported by grants of the German Ministry of Research and Education (BMBF) to the University of M\u00FCnster (01ER0816 and 01ER1506). The PROCAM-2 Study was initiated and conducted by the Leibniz Institute for Arteriosclerosis Research (LIFA) at the University of M\u00FCnster under the leadership of Prof. Dr. G. Assmann. After his retirement all data were transferred to the University of M\u00FCnster for further scientific use. DNA isolation was done later with funds from the dean of the Medical Faculty. Genotyping was enabled through funds from the German Center for Cardiovascular Disease (DZHK). The FOR2107 Marburg study was funded by the German Research Foundation (DFG grants FOR2107 KI588/14-1, and KI588/14-2, and KI588/20-1, KI588/22-1 to Tilo Kircher). Biosamples and corresponding data were sampled, processed and stored in the Marburg Biobank CBBMR. The FOR2107 M\u00FCnster study was funded by the DFG (grants FOR2107 DA1151/5-1 and DA1151/5-2, and SFB-TRR58, Projects C09 and Z02 to Udo Dannlowski) and the Interdisciplinary Center for Clinical Research (IZKF) of the Medical Faculty of the University of M\u00FCnster (grant Dan3/012/17 to Udo Dannlowski). The FOR2107 genetics Mannheim project was funded by the DFG (grants FOR2107 WI3439/3-1 and WI3439/3-2 to Stephanie Witt). The SHIP project is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants No. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide SNP typing in SHIP has been supported by a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. Generation of genome-wide SNP typing in SHIP-TREND-0 was supported by the Federal Ministry of Education and Research (grant No. 03ZIK012). Data collection in SHIP-LEGEND was supported by the German Research Foundation. LG was funded by the DFG (grant No. 403694598). The LIFE-Adult study is supported by LIFE-Leipzig Research Centre for Civilization Diseases, an organizational unit affiliated to the Medical Faculty of the University of Leipzig. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF), by funds of the Free State of Saxony within the framework of the excellence initiative (project numbers 713\u2013241202, 713\u2013241202, 14505/2470, 14575/2470), by funds of the Medical Faculty of Leipzig University, and by funds of the participating institutions.
Funding Information:
SHH is a part-time employee of Life&Brain GmbH. MSc received funding from Pfizer Inc. for a project not related to his research. The rest of the authors have no conflicts of interest relevant to this manuscript to disclose.
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
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.
U2 - 10.1038/s41380-024-02688-1
DO - 10.1038/s41380-024-02688-1
M3 - Article
SN - 1359-4184
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -