View Item 

Show simple item record

Genomeâ wide analyses of psychological resilience in U.S. Army soldiers
dc.contributor.authorStein, Murray B.
dc.contributor.authorChoi, Karmel W.
dc.contributor.authorJain, Sonia
dc.contributor.authorCampbell‐sills, Laura
dc.contributor.authorChen, Chia‐yen
dc.contributor.authorGelernter, Joel
dc.contributor.authorHe, Feng
dc.contributor.authorHeeringa, Steven G.
dc.contributor.authorMaihofer, Adam X.
dc.contributor.authorNievergelt, Caroline
dc.contributor.authorNock, Matthew K.
dc.contributor.authorRipke, Stephan
dc.contributor.authorSun, Xiaoying
dc.contributor.authorKessler, Ronald C.
dc.contributor.authorSmoller, Jordan W.
dc.contributor.authorUrsano, Robert J.
dc.date.accessioned2019-06-20T17:05:14Z
dc.date.availableWITHHELD_14_MONTHS
dc.date.available2019-06-20T17:05:14Z
dc.date.issued2019-07
dc.identifier.citationStein, Murray B.; Choi, Karmel W.; Jain, Sonia; Campbell‐sills, Laura ; Chen, Chia‐yen ; Gelernter, Joel; He, Feng; Heeringa, Steven G.; Maihofer, Adam X.; Nievergelt, Caroline; Nock, Matthew K.; Ripke, Stephan; Sun, Xiaoying; Kessler, Ronald C.; Smoller, Jordan W.; Ursano, Robert J. (2019). "Genomeâ wide analyses of psychological resilience in U.S. Army soldiers." American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 180(5): 310-319.
dc.identifier.issn1552-4841
dc.identifier.issn1552-485X
dc.identifier.urihttps://hdl.handle.net/2027.42/149528
dc.description.abstractThough 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 genomeâ wide association studies (GWASs) of selfâ assessed (by questionnaire) and outcomeâ 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. Selfâ assessed resilience (Nâ =â 11,492) was found to have significant commonâ variant heritability (h2 =â 0.162, seâ =â 0.050, pâ =â 5.37â Ã â 10â 4), and to be significantly negatively genetically correlated with neuroticism (rgâ =â â 0.388, pâ =â .0092). GWAS results from the EUR soldiers revealed a genomeâ wide significant locus on an intergenic region on Chr 4 upstream from doublecortinâ like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [pâ =â 5.65â Ã â 10â 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, kelchâ like family member 36 (KLHL36) was detected at geneâ wise genomeâ wide significance [pâ =â 1.89â Ã â 10â 6]. A polygenic risk score derived from the selfâ assessed resilience GWAS was not significantly associated with outcomeâ based resilience. In very preliminary results, genomeâ wide significant association with outcomeâ based resilience was found for one locus (top SNP: rs12580015 [pâ =â 2.37â Ã â 10â 8]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects (Nâ = 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 stressâ related psychopathology and point to new avenues for therapeutic intervention.
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.othergenetics
dc.subject.othergenomeâ wide association
dc.subject.othermental disorder
dc.subject.otherresilience
dc.subject.otherrisk
dc.titleGenomeâ wide analyses of psychological resilience in U.S. Army soldiers
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMedicine (General)
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/149528/1/ajmgb32730.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/149528/2/ajmgb32730_am.pdf
dc.identifier.doi10.1002/ajmg.b.32730
dc.identifier.sourceAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
dc.identifier.citedreferenceSchwartz, M. L. B., Williams, M. S., & Murray, M. F. ( 2017 ). Adding protective genetic variants to clinical reporting of genomic screening results: Restoring balance. JAMA, 317 ( 15 ), 1527 â 1528.
dc.identifier.citedreferenceKessler, R. C., & Ustun, T. B. ( 2004 ). The World Mental Health (WMH) survey initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). International Journal of Methods in Psychiatric Research, 13 ( 2 ), 93 â 121.
dc.identifier.citedreferenceMajor Depressive Disorder Working Group of the Psychiatric GC, Ripke, S., Wray, N. R., Lewis, C. M., Hamilton, S. P., Weissman, M. M., â ¦ Sullivan, P. F. ( 2013 ). A megaâ analysis of genomeâ wide association studies for major depressive disorder. Molecular Psychiatry, 18 ( 4 ), 497 â 511.
dc.identifier.citedreferenceMcEwen, B. S. ( 2016 ). In pursuit of resilience: Stress, epigenetics, and brain plasticity. Annals of the New York Academy of Sciences, 1373 ( 1 ), 56 â 64.
dc.identifier.citedreferenceMcEwen, B. S., Bowles, N. P., Gray, J. D., Hill, M. N., Hunter, R. G., Karatsoreos, I. N., & Nasca, C. ( 2015 ). Mechanisms of stress in the brain. Nature Neuroscience, 18 ( 10 ), 1353 â 1363.
dc.identifier.citedreferenceMenard, C., Pfau, M. L., Hodes, G. E., & Russo, S. J. ( 2017 ). Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology, 42 ( 1 ), 62 â 80.
dc.identifier.citedreferenceMota, N. P., Han, S., Harpazâ Rotem, I., Maruff, P., Krystal, J. H., Southwick, S. M., â ¦ Pietrzak, R. H. ( 2018 ). Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Depression and Anxiety, 35 ( 2 ), 168 â 177.
dc.identifier.citedreferenceNavrady, L. B., Adams, M. J., SWY, C., Major Depressive Disorder Working Group of the Psychiatric Genomics C, Ritchie, S. J., & McIntosh, A. M. ( 2018 ). Genetic risk of major depressive disorder: The moderating and mediating effects of neuroticism and psychological resilience on clinical and selfâ reported depression. Psychological Medicine, 48 ( 11 ), 1890 â 1899.
dc.identifier.citedreferenceNawabi, H., Belin, S., Cartoni, R., Williams, P. R., Wang, C., Latremoliere, A., â ¦ He, Z. ( 2015 ). Doublecortinâ like kinases promote neuronal survival and induce growth cone reformation via distinct mechanisms. Neuron, 88 ( 4 ), 704 â 719.
dc.identifier.citedreferenceOkbay, A., Baselmans, B. M., De Neve, J. E., Turley, P., Nivard, M. G., Fontana, M. A., â ¦ Cesarini, D. ( 2016 ). Genetic variants associated with subjective wellâ being, depressive symptoms, and neuroticism identified through genomeâ wide analyses. Nature Genetics, 48 ( 6 ), 624 â 633.
dc.identifier.citedreferenceOng, A. D., Bergeman, C. S., Bisconti, T. L., & Wallace, K. A. ( 2006 ). Psychological resilience, positive emotions, and successful adaptation to stress in later life. Journal of Personality and Social Psychology, 91 ( 4 ), 730 â 749.
dc.identifier.citedreferenceOtowa, T., Hek, K., Lee, M., Byrne, E. M., Mirza, S. S., Nivard, M. G., â ¦ Hettema, J. M. ( 2016 ). Metaâ analysis of genomeâ wide association studies of anxiety disorders. Molecular Psychiatry, 21 ( 10 ), 1391 â 1399.
dc.identifier.citedreferencePfau, M. L., & Russo, S. J. ( 2015 ). Peripheral and central mechanisms of stress resilience. Neurobiology Stress, 1, 66 â 79.
dc.identifier.citedreferencePietrzak, R. H., Feder, A., Singh, R., Schechter, C. B., Bromet, E. J., Katz, C. L., â ¦ Southwick, S. M. ( 2014 ). Trajectories of PTSD risk and resilience in world trade center responders: An 8â year prospective cohort study. Psychological Medicine, 44 ( 1 ), 205 â 219.
dc.identifier.citedreferencePurcell, S., Neale, B., Toddâ Brown, K., Thomas, L., Ferreira, M. A., Bender, D., â ¦ Sham, P. C. ( 2007 ). PLINK: A tool set for wholeâ genome association and populationâ based linkage analyses. American Journal of Human Genetics, 81 ( 3 ), 559 â 575.
dc.identifier.citedreferenceRietveld, C. A., Cesarini, D., Benjamin, D. J., Koellinger, P. D., De Neve, J. E., Tiemeier, H., â ¦ Bartels, M. ( 2013 ). Molecular genetics and subjective wellâ being. Proceedings of the National Academy of Sciences of the United States of America, 110 ( 24 ), 9692 â 9697.
dc.identifier.citedreferenceRosellini, A. J., Stein, M. B., Benedek, D. M., Bliese, P. D., Chiu, W. T., Hwang, I., â ¦ Kessler, R. C. ( 2018 ). Predeployment predictors of psychiatric disorderâ symptoms and interpersonal violence during combat deployment. Depression and Anxiety, 35 ( 11 ), 1073 â 1080.
dc.identifier.citedreferenceShin, E., Kashiwagi, Y., Kuriu, T., Iwasaki, H., Tanaka, T., Koizumi, H., â ¦ Okabe, S. ( 2013 ). Doublecortinâ like kinase enhances dendritic remodelling and negatively regulates synapse maturation. Nature Communications, 4, 1440.
dc.identifier.citedreferenceSmoller, J. W., Andreassen, O. A., Edenberg, H. J., Faraone, S. V., Glatt, S. J., & Kendler, K. S. ( 2019 ). Psychiatric genetics and the structure of psychopathology. Molecular Psychiatry, 24 ( 3 ), 409 â 420.
dc.identifier.citedreferenceSniekers, S., Stringer, S., Watanabe, K., Jansen, P. R., Coleman, J. R. I., Krapohl, E., â ¦ Posthuma, D. ( 2017 ). Genomeâ wide association metaâ analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nature Genetics, 49 ( 7 ), 1107 â 1112.
dc.identifier.citedreferenceSouthwick, S. M., & Charney, D. S. ( 2012 ). The science of resilience: Implications for the prevention and treatment of depression. Science, 338 ( 6103 ), 79 â 82.
dc.identifier.citedreferenceStein, M. B., Campbellâ Sills, L., & Gelernter, J. ( 2009 ). Genetic variation in 5HTTLPR is associated with emotional resilience. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 150B ( 7 ), 900 â 906.
dc.identifier.citedreferenceStein, M. B., Chen, C. Y., Ursano, R. J., Cai, T., Gelernter, J., Heeringa, S. G., â ¦ Resilience in Servicemembers C. ( 2016 ). Genomeâ wide association studies of posttraumatic stress disorder in 2 cohorts of US Army soldiers. JAMA Psychiatry, 73 ( 7 ), 695 â 704.
dc.identifier.citedreferenceStein, M. B., Kessler, R. C., Heeringa, S. G., Jain, S., Campbellâ Sills, L., Colpe, L. J., â ¦ Sc, A. ( 2015 ). Prospective longitudinal evaluation of the effect of deploymentâ acquired traumatic brain injury on posttraumatic stress and related disorders: Results from the Army study to assess risk and resilience in Servicemembers (Army STARRS). The American Journal of Psychiatry, 172 ( 11 ), 1101 â 1111.
dc.identifier.citedreferenceStein, M. B., & Smoller, J. W. ( 2018 ). Precision psychiatryâ will genomic medicine lead the way? JAMA Psychiatry, 75 ( 7 ), 663 â 664.
dc.identifier.citedreferenceter Heegde, F., De Rijk, R. H., & Vinkers, C. H. ( 2015 ). The brain mineralocorticoid receptor and stress resilience. Psychoneuroendocrinology, 52, 92 â 110.
dc.identifier.citedreferenceUhlen, M., Fagerberg, L., Hallstrom, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., â ¦ Ponten, F. ( 2015 ). Proteomics. Tissueâ based map of the human proteome. Science, 347 ( 6220 ), 1260419.
dc.identifier.citedreferenceUrsano, R. J., Colpe, L. J., Heeringa, S. G., Kessler, R. C., Schoenbaum, M., Stein, M. B., & Army, S. ( 2014 ). The Army study to assess risk and resilience in servicemembers (Army STARRS). Psychiatry, 77 ( 2 ), 107 â 119.
dc.identifier.citedreferenceWaaktaar, T., & Torgersen, S. ( 2012 ). Genetic and environmental causes of variation in trait resilience in young people. Behavior Genetics, 42 ( 3 ), 366 â 377.
dc.identifier.citedreferenceWatanabe, K., Taskesen, E., van Bochoven, A., & Posthuma, D. ( 2017 ). Functional mapping and annotation of genetic associations with FUMA. Nature Communications, 8 ( 1 ), 1826.
dc.identifier.citedreferenceWingo, A. P., Almli, L. M., Stevens, J. S., Jovanovic, T., Wingo, T. S., Tharp, G., â ¦ Ressler, K. J. ( 2017 ). Genomeâ wide association study of positive emotion identifies a genetic variant and a role for microRNAs. Molecular Psychiatry, 22 ( 5 ), 774 â 783.
dc.identifier.citedreferenceWolf, E. J., Miller, M. W., Sullivan, D. R., Amstadter, A. B., Mitchell, K. S., Goldberg, J., & Magruder, K. M. ( 2018 ). A classical twin study of PTSD symptoms and resilience: Evidence for a single spectrum of vulnerability to traumatic stress. Depression and Anxiety, 35 ( 2 ), 132 â 139.
dc.identifier.citedreferenceYang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. ( 2011 ). GCTA: A tool for genomeâ wide complex trait analysis. American Journal of Human Genetics, 88 ( 1 ), 76 â 82.
dc.identifier.citedreferenceYung, G., & Lin, X. ( 2016 ). Validity of using ad hoc methods to analyze secondary traits in caseâ control association studies. Genetic Epidemiology, 40 ( 8 ), 732 â 743.
dc.identifier.citedreferenceZautra, A. J., Johnson, L. M., & Davis, M. C. ( 2005 ). Positive affect as a source of resilience for women in chronic pain. Journal of Consulting and Clinical Psychology, 73 ( 2 ), 212 â 220.
dc.identifier.citedreferenceZheng, J., Erzurumluoglu, A. M., Elsworth, B. L., Kemp, J. P., Howe, L., Haycock, P. C., â ¦ Neale, B. M. ( 2017 ). LD hub: A centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics, 33 ( 2 ), 272 â 279.
dc.identifier.citedreferencede Leeuw, C. A., Mooij, J. M., Heskes, T., & Posthuma, D. ( 2015 ). MAGMA: Generalized geneâ set analysis of GWAS data. PLoS Computational Biology, 11 ( 4 ), e1004219.
dc.identifier.citedreferenceAmstadter, A. B., Myers, J. M., & Kendler, K. S. ( 2014 ). Psychiatric resilience: Longitudinal twin study. The British Journal of Psychiatry, 205 ( 4 ), 275 â 280.
dc.identifier.citedreferenceBenjet, C., Bromet, E., Karam, E. G., Kessler, R. C., McLaughlin, K. A., Ruscio, A. M., â ¦ Koenen, K. C. ( 2016 ). The epidemiology of traumatic event exposure worldwide: Results from the World Mental Health Survey Consortium. Psychological Medicine, 46 ( 2 ), 327 â 343.
dc.identifier.citedreferenceBinder, E. B. ( 2017 ). Dissecting the molecular mechanisms of gene x environment interactions: Implications for diagnosis and treatment of stressâ related psychiatric disorders. European Journal of Psychotraumatology, 8 ( Suppl. 5 ), 1412745.
dc.identifier.citedreferenceBonanno, G. A., Westphal, M., & Mancini, A. D. ( 2011 ). Resilience to loss and potential trauma. Annual Review of Clinical Psychology, 7, 511 â 535.
dc.identifier.citedreferenceBruenig, D., Morris, C. P., Mehta, D., Harvey, W., Lawford, B., Young, R. M., & Voisey, J. ( 2017 ). Nitric oxide pathway genes (NOS1AP and NOS1) are involved in PTSD severity, depression, anxiety, stress and resilience. Gene, 625, 42 â 48.
dc.identifier.citedreferenceBulikâ Sullivan, B., Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P. R., â ¦ Neale, B. M. ( 2015 ). An atlas of genetic correlations across human diseases and traits. Nature Genetics, 47 ( 11 ), 1236 â 1241.
dc.identifier.citedreferenceCampbellâ Sills, L., Kessler, R. C., Ursano, R. J., Sun, X., Taylor, C. T., Heeringa, S. G., â ¦ Stein, M. B. ( 2018 ). Predictive validity and correlates of selfâ assessed resilience among U.S. Army soldiers. Depression and Anxiety, 35 ( 2 ), 122 â 131.
dc.identifier.citedreferenceCampbellâ Sills, L., & Stein, M. B. ( 2007 ). Psychometric analysis and refinement of the Connorâ davidson resilience scale (CDâ RISC): Validation of a 10â item measure of resilience. Journal of Traumatic Stress, 20 ( 6 ), 1019 â 1028.
dc.identifier.citedreferenceChang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. ( 2015 ). Secondâ generation PLINK: Rising to the challenge of larger and richer datasets. GigaScience, 4, 7.
dc.identifier.citedreferenceChmitorz, A., Kunzler, A., Helmreich, I., Tuscher, O., Kalisch, R., Kubiak, T., â ¦ Lieb, K. ( 2018 ). Intervention studies to foster resilienceâ A systematic review and proposal for a resilience framework in future intervention studies. Clinical Psychology Review, 59, 78 â 100.
dc.identifier.citedreferenceColodroâ Conde, L., Couvyâ Duchesne, B., Zhu, G., Coventry, W. L., Byrne, E. M., Gordon, S., â ¦ Martin, N. G. ( 2018 ). A direct test of the diathesisâ stress model for depression. Molecular Psychiatry, 23, 1590 â 1596.
dc.identifier.citedreferenceConnor, K. M., & Davidson, J. R. ( 2003 ). Development of a new resilience scale: The Connorâ Davidson Resilience Scale (CDâ RISC). Depression and Anxiety, 18 ( 2 ), 76 â 82.
dc.identifier.citedreferenceDomingue, B. W., Liu, H., Okbay, A., & Belsky, D. W. ( 2017 ). Genetic heterogeneity in depressive symptoms following the death of a spouse: Polygenic score analysis of the U.S. health and retirement study. The American Journal of Psychiatry, 174 ( 10 ), 963 â 970.
dc.identifier.citedreferenceEuesden, J., Lewis, C. M., & O’Reilly, P. F. ( 2015 ). PRSice: Polygenic risk score software. Bioinformatics, 31 ( 9 ), 1466 â 1468.
dc.identifier.citedreferenceFeder, A., Horn, S. R., Haglund, M., Southwick, S. M., & Charney, D. S. ( 2018 ). The neurobiology of resilience. In D. S. Charney, P. B. Sklar, J. D. Buxbaum, & E. J. Nestler (Eds.), Charney and Nestler’s neurobiology of mental illness (pp. 487 â 512 ). New York: Oxford University Press.
dc.identifier.citedreferenceFredrickson, B. L., Tugade, M. M., Waugh, C. E., & Larkin, G. R. ( 2003 ). What good are positive emotions in crises? A prospective study of resilience and emotions following the terrorist attacks on the United States on September 11th, 2001. Journal of Personality and Social Psychology, 84 ( 2 ), 365 â 376.
dc.identifier.citedreferenceGalatzerâ Levy, I. R., Huang, S. H., & Bonanno, G. A. ( 2018 ). Trajectories of resilience and dysfunction following potential trauma: A review and statistical evaluation. Clinical Psychology Review, 63, 41 â 55.
dc.identifier.citedreferenceHaworth, C. M., Nelson, S. K., Layous, K., Carter, K., Jacobs Bao, K., Lyubomirsky, S., & Plomin, R. ( 2016 ). Stability and change in genetic and environmental influences on wellâ being in response to an intervention. PLoS One, 11 ( 5 ), e0155538.
dc.identifier.citedreferenceHibar, D. P., Stein, J. L., Renteria, M. E., Ariasâ Vasquez, A., Desrivieres, S., Jahanshad, N., â ¦ Medland, S. E. ( 2015 ). Common genetic variants influence human subcortical brain structures. Nature, 520 ( 7546 ), 224 â 229.
dc.identifier.citedreferenceHowlett, J. R., & Stein, M. B. ( 2016 ). Prevention of trauma and stressorâ related disorders: A review. Neuropsychopharmacology, 41 ( 1 ), 357 â 369.
dc.identifier.citedreferenceJones, R. M., Cadby, G., Melton, P. E., Abraham, L. J., Whitehouse, A. J., & Moses, E. K. ( 2013 ). Genomeâ wide association study of autisticâ like traits in a general population study of young adults. Frontiers in Human Neuroscience, 7, 658.
dc.identifier.citedreferenceKalisch, R., Baker, D. G., Basten, U., Boks, M. P., Bonanno, G. A., Brummelman, E., â ¦ Kleim, B. ( 2017 ). The resilience framework as a strategy to combat stressâ related disorders. Nature Human Behaviour, 1 ( 11 ), 784 â 790.
dc.identifier.citedreferenceKalisch, R., Muller, M. B., & Tuscher, O. ( 2015 ). A conceptual framework for the neurobiological study of resilience. The Behavioral and Brain Sciences, 38, e92.
dc.identifier.citedreferenceKerjan, G., Koizumi, H., Han, E. B., Dube, C. M., Djakovic, S. N., Patrick, G. N., â ¦ Gleeson, J. G. ( 2009 ). Mice lacking doublecortin and doublecortinâ like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures. Proceedings of the National Academy of Sciences of the United States of America, 106 ( 16 ), 6766 â 6771.
dc.owningcollnameInterdisciplinary and Peer-Reviewed


Files in this item

Name:
ajmgb32730.pdf
Size:
1.510MB
Format:
PDF
View/Open
Name:
ajmgb32730_am.pdf
Size:
457.5KB
Format:
PDF
View/Open

Show simple item record

Remediation of Harmful Language

The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.

Accessibility

If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.