The brief resilience scale: a genome-wide association study in the UK Biobank

Some individuals exposed to traumatic stressors develop psychiatric disorders while others remain resilient. The Brief Resilience Scale (BRS) assesses the ability to "bounce back" from stress and is a widely used measure of trait resilience. We performed the first genome-wide association study of BRS in the UK Biobank (UKB). Beginning 2022, a subset of UKB participants completed an on-line mental-health questionnaire that included the six-item BRS. BRS data and genome-wide typing and imputation were available for 124,774 participants of European ancestry. Genome-wide linear tests of BRS were performed, followed by SNP-based heritability and cross-trait genetic correlation analyses. Nominally significant loci (P < 5 × 10−6) were followed up for candidate gene mapping. SNP-based heritability of BRS was 7.3% and strong genetic correlations (rg) were observed with neuroticism (rg, − 0.70 to − 0.44), depression (rg, − 0.63 to − 0.37) and anxiety (rg, − 0.81 to − 0.46). Three loci met genome-wide significance (P < 5 × 10−8, near VRK2, TNKS/MSRA and RAB36) and 29 loci met nominal significance (P < 5 × 10−6). None of these were replicated in prior GWAS using different measures of resilience. The strongest candidate genes prioritized on the basis of both functional and biological evidence include VRK2 (2p16.1) (previously associated with neuropsychiatric disorders) and MSRA (8p23.1) (reduces methionine sulfoxide to methionine). Others at nominally significant loci include SLC6A9 (1p34.1) (encodes a glycine transporter), NPY (7p15.2) (involved in stress response), CADPS2 (7q31.32) (involved in synaptic vesicle exocytosis), and PCDH9 (13q21.32) (involved in neural tissue cell adhesion). Our findings provide further support for a genetic basis to trait resilience and one shared with psychiatric disorders and personality traits including depression, anxiety, and neuroticism. Our promising loci warrant replication but offer new biological insight to resilience.