Genome‐wide analyses of psychological resilience in U.S. Army soldiers. Issue 5 (13th May 2019) - Stein, Murray B.
Abstract: Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome‐wide association studies (GWASs) of self‐assessed (by questionnaire) and outcome‐based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self‐assessed resilience ( N = 11, 492) was found to have significant common‐variant heritability ( h 2 = 0.162, se = 0.050, p = 5.37 × 10 −4 ), and to be significantly negatively genetically correlated with neuroticism ( r g = −0.388, p = .0092). GWAS results from the EUR soldiers revealed a genome‐wide significant locus on an intergenic region on Chr 4 upstream from doublecortin‐like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [ p = 5.65 × 10 −9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch‐like family member 36 (KLHL36) was detected at gene‐wise genome‐wide significance [ p = 1.89 × 10 −6 ]. A polygenic risk score derived from the self‐assessed resilience GWAS was not significantly associated with outcome‐based resilience. In very preliminary results, genome‐wide significant association with outcome‐based resilience was found for one locus (top SNP: rs12580015 [ p = 2.37 × 10 −8 ]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects ( N = 581) exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress‐related psychopathology and point to new avenues for therapeutic intervention.