Genome-wide analyses of psychological resilience in U.S. Army soldiers

doi:10.1002/ajmg.b.32730

. 2019 Jul;180(5):310-319.

doi: 10.1002/ajmg.b.32730. Epub 2019 May 13.

Genome-wide analyses of psychological resilience in U.S. Army soldiers

Murray B Stein^{1

2

3}, Karmel W Choi⁴, Sonia Jain², Laura Campbell-Sills¹, Chia-Yen Chen^{4

5

6}, Joel Gelernter^{7

8

9}, Feng He², Steven G Heeringa¹⁰, Adam X Maihofer¹, Caroline Nievergelt¹, Matthew K Nock¹¹, Stephan Ripke^{5

12

13}, Xiaoying Sun², Ronald C Kessler¹⁴, Jordan W Smoller^{4

5

6}, Robert J Ursano¹⁵

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, California.
² Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
³ Psychiatry Service, VA San Diego Healthcare System, San Diego, California.
⁴ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
⁵ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
⁶ Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
⁷ Department of Psychiatry, Yale University, New Haven, Connecticut.
⁸ VA Connecticut Healthcare System, West Haven, Connecticut.
⁹ Departments of Genetics and Neurobiology, Yale University, New Haven, Connecticut.
¹⁰ Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
¹¹ Department of Psychology, Harvard University, Cambridge, Massachusetts.
¹² Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston MA 02114, USA.
¹³ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin 10117, Germany.
¹⁴ Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
¹⁵ Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

PMID: 31081985
PMCID: PMC6551278
DOI: 10.1002/ajmg.b.32730

Free PMC article

Genome-wide analyses of psychological resilience in U.S. Army soldiers

Murray B Stein et al. Am J Med Genet B Neuropsychiatr Genet. 2019 Jul.

Free PMC article

. 2019 Jul;180(5):310-319.

doi: 10.1002/ajmg.b.32730. Epub 2019 May 13.

Authors

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, California.
² Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.
³ Psychiatry Service, VA San Diego Healthcare System, San Diego, California.
⁴ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
⁵ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
⁶ Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
⁷ Department of Psychiatry, Yale University, New Haven, Connecticut.
⁸ VA Connecticut Healthcare System, West Haven, Connecticut.
⁹ Departments of Genetics and Neurobiology, Yale University, New Haven, Connecticut.
¹⁰ Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
¹¹ Department of Psychology, Harvard University, Cambridge, Massachusetts.
¹² Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston MA 02114, USA.
¹³ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin 10117, Germany.
¹⁴ Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
¹⁵ Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

PMID: 31081985
PMCID: PMC6551278
DOI: 10.1002/ajmg.b.32730

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 (h² = 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.

Keywords: genetics; genome-wide association; mental disorder; resilience; risk.

Figures

**Figure 1**
Cohorts Used for Analysis of Self-assessed and Outcome-based Resilience.

**Figure 2**
Manhattan plot of NSS1, NSS2, and PPDS Self-Assessed Resilience Genome-Wide Association Study (GWAS) in Soldiers of European (EUR) Ancestry

**Figure 3**
Locus-zoom plot showing region on Chr 4 containing the genome-wide significant markers in the NSS1, NSS2, and PPDS Self-Assessed Resilience EUR GWAS

See this image and copyright information in PMC

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