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bioRxiv · 10.1101/516716

Genomewide Analyses of Psychological Resilience in US Army Soldiers

Stein, M.·Choi, K. W.·Jain, S.·Campbell-Sills, L.·Chen, C.-Y.·Gelernter, J.·He, F.·Heeringa, S. G.·Maihofer, A. X.·Nievergelt, C. M.·Nock, M. K.·Ripke, S.·Sun, X.·Kessler, R. C.·Smoller, J. W.·Ursano, R. J.
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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 genomewide association studies (GWAS) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from pre- to post-deployment) resilience among European (EUR) ancestry soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). Self-assessed resilience (N=11,492) was found to have significant common-variant heritability (h2=0.162, se=0.050, p=5.37e-4), and to be significantly negatively genetically correlated with neuroticism (rg= -0.388, p=0.0092). GWAS results from the EUR soldiers revealed a genomewide significant locus (4 SNPs in LD; top SNP: rs4260523, p=5.654e-09) on an intergenic region on Chr 4 upstream from DCLK2 (Doublecortin-Like Kinase 2), a member of the doublecortin (DCX) family of kinases that promote survival and regeneration of injured neurons. A second gene, KLHL36 (Kelch Like Family Member 36) was detected at gene-wise genomewide significance (p=1.89e-06). A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genomewide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015) on Chr 12 downstream from SLC15A5 (solute carrier family 15 member 5) in the small group (N=581) of subjects 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 potentially point to new avenues for therapeutic intervention.

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Stein, M., Choi, K. W., Jain, S., Campbell-Sills, L., Chen, C.-Y., Gelernter, J., He, F., Heeringa, S. G., Maihofer, A. X., Nievergelt, C. M., Nock, M. K., Ripke, S., Sun, X., Kessler, R. C., Smoller, J. W., Ursano, R. J.. 2019-01-20. Genomewide Analyses of Psychological Resilience in US Army Soldiers. https://doi.org/10.1101/516716

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