Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD

Abstract

Many mental disorders represent the extremes of the normal distribution of traits, which are related to multiple cognitive and emotional dimensions. By performing whole-exome sequencing of healthy, young subjects with extremely high versus extremely low aversive memory performance, we identified TROVE2 as a gene implicated in emotional memory in health and disease. TROVE2 encodes Ro60, a broadly expressed RNA-binding protein implicated in the regulation of inflammatory gene expression and autoimmunity. A regulatory TROVE2 variant was linked to higher emotional memory capacity and higher emotional memory-related brain activation in healthy subjects. In addition, TROVE2 was associated with traumatic memory and the frequency of post-traumatic stress disorder in genocide survivors.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Frequency histogram of aversive memory performance in 3,418 healthy, young adults.
Figure 2: Sequencing results of TROVE2 (positions according to the GRCh37/hg19 coordinates).
Figure 3: TROVE2 rs72740218 genotype-dependent differences in brain activity related to successful memory encoding of aversive stimuli compared with neutral stimuli in 1,258 healthy young subjects.
Figure 4: Association of TROVE2 SNPs rs72740218 and rs6692342 in the human frontal cortex.
Figure 5: Schematic representation of selected TROVE2 RefSeq transcript variants (positions according to GRCh37/hg19 coordinates).

References

  1. 1

    McGaugh, J. L . in Memory and Emotion (Weidenfeld and Nicolson, 2003).

    Google Scholar 

  2. 2

    Pitman, R. K. Post-traumatic stress disorder, hormones, and memory. Biol. Psychiatry 26, 221–223 (1989).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  3. 3

    Phelps, E. A. & LeDoux, J. E. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48, 175–187 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4

    Brewin, C. R., Dalgleish, T. & Joseph, S. A dual representation theory of posttraumatic stress disorder. Psychol. Rev. 103, 670–686 (1996).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  5. 5

    Brewin, C. R., Gregory, J. D., Lipton, M. & Burgess, N. Intrusive images in psychological disorders: characteristics, neural mechanisms, and treatment implications. Psychol. Rev. 117, 210–232 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6

    de Quervain, D. J. et al. A deletion variant of the α2b-adrenoceptor is related to emotional memory in Europeans and Africans. Nat. Neurosci. 10, 1137–1139 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7

    de Quervain, D. J. et al. PKCα is genetically linked to memory capacity in healthy subjects and to risk for posttraumatic stress disorder in genocide survivors. Proc. Natl Acad. Sci. USA 109, 8746–8751 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8

    Todd, R. M. et al. Deletion variant in the ADRA2B gene increases coupling between emotional responses at encoding and later retrieval of emotional memories. Neurobiol. Learn Mem. 112, 222–229 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9

    Todd, R. M., Palombo, D. J., Levine, B. & Anderson, A. K. Genetic differences in emotionally enhanced memory. Neuropsychologia 49, 734–744 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  10. 10

    Papassotiropoulos, A. et al. Human genome-guided identification of memory-modulating drugs. Proc. Natl Acad. Sci. USA 110, E4369–E4374 (2013).

    CAS  PubMed  Article  Google Scholar 

  11. 11

    Ackermann, S., Heck, A., Rasch, B., Papassotiropoulos, A. & de Quervain, D. J. The BclI polymorphism of the glucocorticoid receptor gene is associated with emotional memory performance in healthy individuals. Psychoneuroendocrinology 38, 1203–1207 (2013).

    CAS  PubMed  Article  Google Scholar 

  12. 12

    Gibbs, A. A., Bautista, C. E., Mowlem, F. D., Naudts, K. H. & Duka, T. Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers. J. Neurosci. 33, 17023–17028 (2013).

    CAS  PubMed  Article  Google Scholar 

  13. 13

    Cheung, J. & Bryant, R. A. FKBP5 risk alleles and the development of intrusive memories. Neurobiol. Learn. Mem. 125, 258–264 (2015).

    CAS  PubMed  Article  Google Scholar 

  14. 14

    Wilker, S., Elbert, T. & Kolassa, I.-T. The downside of strong emotional memories: how human memory-related genes influence the risk for posttraumatic stress disorder—a selective review. Neurobiol. Learn. Mem. 112, 75–86 (2014).

    PubMed  Article  Google Scholar 

  15. 15

    Kiezun, A. et al. Exome sequencing and the genetic basis of complex traits. Nat. Genet. 44, 623–630 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16

    Wang, Z., Liu, X., Yang, B. Z. & Gelernter, J. The role and challenges of exome sequencing in studies of human diseases. Front. Genet. 4, 160 (2013).

    PubMed  PubMed Central  Google Scholar 

  17. 17

    Peloso, G. M. et al. Phenotypic extremes in rare variant study designs. Eur. J. Hum. Genet. 24, 924–930 (2016).

    PubMed  Article  Google Scholar 

  18. 18

    Li, D., Lewinger, J. P., Gauderman, W. J., Murcray, C. E. & Conti, D. Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies. Genet. Epidemiol. 35, 790–799 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  19. 19

    Auer, P. L. & Lettre, G. Rare variant association studies: considerations, challenges and opportunities. Genome Med. 7, 16 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  20. 20

    Guey, L. T. et al. Power in the phenotypic extremes: a simulation study of power in discovery and replication of rare variants. Genet. Epidemiol. 35, 236–246 (2011).

    PubMed  Google Scholar 

  21. 21

    Emond, M. J. et al. Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis. Nat. Genet. 44, 886–889 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22

    Lee, S. et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am. J. Hum. Genet. 91, 224–237 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23

    Ramasamy, A. et al. Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat. Neurosci. 17, 1418–1428 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24

    Trabzuni, D. et al. Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies. J. Neurochem. 119, 275–282 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25

    LaBar, K. S. & Cabeza, R. Cognitive neuroscience of emotional memory. Nat. Rev. Neurosci. 7, 54–64 (2006).

    CAS  PubMed  Article  Google Scholar 

  26. 26

    Buchanan, T. W. Retrieval of emotional memories. Psychol. Bull. 133, 761–779 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27

    Stein, M. B., Jang, K. L., Taylor, S., Vernon, P. A. & Livesley, W. J. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. Am. J. Psychiatry 159, 1675–1681 (2002).

    PubMed  Article  Google Scholar 

  28. 28

    Foa, E. B., Cashman, L., Jaycox, L. & Perry, K. The validation of a self-report measure of posttraumatic stress disorder: The posttraumatic diagnostic scale. Psychol. Assess. 9, 445–451 (1997).

    Article  Google Scholar 

  29. 29

    Hawrylycz, M. J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30

    Speir, M. L. et al. The UCSC genome browser database: 2016 update. Nucleic Acids Res. 44, D717–D725 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  31. 31

    UniProt, C. UniProt: a hub for protein information. Nucleic Acids Res. 43, D204–D212 (2015).

    Article  CAS  Google Scholar 

  32. 32

    Etkin, A., Egner, T. & Kalisch, R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn. Sci. 15, 85–93 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  33. 33

    Murty, V. P., Ritchey, M., Adcock, R. A. & LaBar, K. S. fMRI studies of successful emotional memory encoding: a quantitative meta-analysis. Neuropsychologia 48, 3459–3469 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34

    Thomaes, K. et al. Increased anterior cingulate cortex and hippocampus activation in complex PTSD during encoding of negative words. Soc. Cogn. Affect. Neurosci. 8, 190–200 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  35. 35

    Lanius, R. A. et al. Emotion modulation in PTSD: clinical and neurobiological evidence for a dissociative subtype. Am. J. Psychiatry 167, 640–647 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  36. 36

    Schulte-Pelkum, J., Fritzler, M. & Mahler, M. Latest update on the Ro/SS-A autoantibody system. Autoimmun. Rev. 8, 632–637 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  37. 37

    Alspaugh, M. & Maddison, P. Resolution of the identity of certain antigen–antibody systems in systemic lupus erythematosus and Sjogren’s syndrome: an interlaboratory collaboration. Arthritis Rheum. 22, 796–798 (1979).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  38. 38

    Clark, G., Reichlin, M. & Tomasi, T. B. Jr. Characterization of a soluble cytoplasmic antigen reactive with sera from patients with systemic lupus erythmatosus. J. Immunol. 102, 117–122 (1969).

    CAS  PubMed  Google Scholar 

  39. 39

    Hung, T. et al. The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression. Science 350, 455–459 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40

    O’Donovan, A. et al. Elevated risk for autoimmune disorders in Iraq and Afghanistan veterans with posttraumatic stress disorder. Biol. Psychiatry 77, 365–374 (2015).

    PubMed  Article  Google Scholar 

  41. 41

    Stein, M. B. et al. Genome-wide association studies of posttraumatic stress disorder in 2 cohorts of US army soldiers. JAMA Psychiatry 73, 695–704 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  42. 42

    Eraly, S. A. et al. Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk. JAMA Psychiatry 71, 423–431 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43

    Michopoulos, V. et al. Association of CRP genetic variation and CRP level with elevated PTSD symptoms and physiological responses in a civilian population with high levels of trauma. Am. J. Psychiatry 172, 353–362 (2015).

    PubMed  Article  Google Scholar 

  44. 44

    Smith, A. K. et al. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B, 700–708 (2011).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  45. 45

    Lindqvist, D. et al. Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. Brain Behav. Immun. 42, 81–88 (2014).

    PubMed  Article  Google Scholar 

  46. 46

    Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337–341 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47

    Derecki, N. C. et al. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J. Exp. Med. 207, 1067–1080 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48

    Filiano, A. J. et al. Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature 535, 425–429 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49

    Kilaru, V. et al. Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder. Transl. Psychiatry 6, e820 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50

    Ashley-Koch, A. E. et al. Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq–Afghanistan era veterans. J. Affect. Disord. 184, 225–234 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  51. 51

    Nievergelt, C. M. et al. Genomic predictors of combat stress vulnerability and resilience in U.S. marines: a genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene. Psychoneuroendocrinology 51, 459–471 (2015).

    Google Scholar 

  52. 52

    Almli, L. M. et al. A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces. Am. J. Med. Genet. B Neuropsychiatr. Genet. 168B, 327–336 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  53. 53

    Logue, M. W. et al. A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Mol. Psychiatry 18, 937–942 (2013).

    CAS  PubMed  Article  Google Scholar 

  54. 54

    Xie, P. et al. Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder. Biol. Psychiatry 74, 656–663 (2013).

    CAS  PubMed  Article  Google Scholar 

  55. 55

    Guffanti, G. et al. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women. Psychoneuroendocrinology 38, 3029–3038 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56

    Logue, M. W. et al. The psychiatric genomics consortium posttraumatic stress disorder workgroup: posttraumatic stress disorder enters the age of large-scale genomic collaboration. Neuropsychopharmacology 40, 2287–2297 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57

    Rangaraju, S. et al. Mood, stress and longevity: convergence on ANK3. Mol. Psychiatry 21, 1037–1049 (2016).

    CAS  PubMed  Article  Google Scholar 

  58. 58

    Papassotiropoulos, A. & de Quervain, D. J. Failed drug discovery in psychiatry: time for human genome-guided solutions. Trends Cogn. Sci. 19, 183–187 (2015).

    PubMed  Article  Google Scholar 

  59. 59

    Lang, P. J., Bradley, M. M. & Cuthbert, B. N. International Affective Pictures System (IAPS): Affective Ratings of Pictures and Instruction Manual (Univ. Florida, 2008).

  60. 60

    Wood, A. R. et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 46, 1173–1186 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. 61

    Locke, A. E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197–206 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. 62

    Heck, A. et al. Genetic analysis of association between calcium signaling and hippocampal activation, memory performance in the young and old, and risk for sporadic Alzheimer disease. JAMA Psychiatry 72, 1029–1036 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  63. 63

    Heck, A. et al. Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity. Neuron 81, 1203–1213 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64

    Hauer, D. et al. Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy. Crit. Care Med. 39, 643–650 (2011).

    CAS  PubMed  Article  Google Scholar 

  65. 65

    Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66

    Price, A. L. et al. Long-range LD can confound genome scans in admixed populations. Am. J. Hum. Genet. 83, 132–135 (2008); author reply 83, 135–139 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67

    Sekhon, J. S. Multivariate and propensity score matching software with automated balance optimization: the matching package for R. J. Stat. Softw. 42, 1–52 (2011).

    Article  Google Scholar 

  68. 68

    Reisberg, D. & Heuer, F. in Memory and Emotion (eds Reisberg, D. & Hertel, P. ) 3–40 (Oxford Univ. Press, 2004).

    Google Scholar 

  69. 69

    Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70

    Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71

    McKenna, A. et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72

    Van der Auwera, G. A. et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr. Protoc. Bioinformatics 43, 11.10.1–11.10.33 (2013).

    Google Scholar 

  73. 73

    DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. 74

    Guo, Y., Ye, F., Sheng, Q., Clark, T. & Samuels, D. C. Three-stage quality control strategies for DNA re-sequencing data. Brief. Bioinform. 15, 879–889 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75

    McKernan, K. J. et al. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res. 19, 1527–1541 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. 76

    Schuster, S. C. et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 463, 943–947 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77

    Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 6, 80–92 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78

    Madsen, B. E. & Browning, S. R. A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet. 5, e1000384 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  79. 79

    Price, A. L. et al. Pooled association tests for rare variants in exon-resequencing studies. Am. J. Hum. Genet. 86, 832–838 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  80. 80

    Lee, S., Abecasis, G. R., Boehnke, M. & Lin, X. Rare-variant association analysis: study designs and statistical tests. Am. J. Hum. Genet. 95, 5–23 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81

    Desikan, R. S. et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31, 968–980 (2006).

    PubMed  PubMed Central  Article  Google Scholar 

  82. 82

    Damasio, H & Damasio, A. R. Lesion Analysis in Neuropsychology, (Oxford Univ. Press, 1989).

    Google Scholar 

  83. 83

    Ertl, V. et al. Validation of a mental health assessment in an African conflict population. Psychol. Assess. 22, 318–324 (2010).

    PubMed  Article  Google Scholar 

  84. 84

    Wilker, S. et al. How to quantify exposure to traumatic stress? Reliability and predictive validity of measures for cumulative trauma exposure in a post-conflict population. Eur. J. Psychotraumatol. 6, 28306 (2015).

    PubMed  Article  Google Scholar 

  85. 85

    Onyut, L. P. et al. Trauma, poverty and mental health among Somali and Rwandese refugees living in an African refugee settlement — an epidemiological study. Confl. Health 3, 6 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  86. 86

    Kolassa, I.-T., Kolassa, S., Ertl, V., Papassotiropoulos, A. & De Quervain, D. J. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biol. Psychiatry 67, 304–308 (2010).

    CAS  PubMed  Article  Google Scholar 

  87. 87

    Neuner, F. et al. Psychological trauma and evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among West Nile refugees. BMC Psychiatry 4, 34 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

This work was funded by the University of Basel, the Swiss National Science Foundation (grants 163434, 147570 and 159740 to D.J.-F.d.Q. and A.P.), the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement 602450 (IMAGEMEND; grant to A.P. and D.J.-F.d.Q.), the Novartis Foundation for medical-biological Research (grant 15C219 to A.P.), and by the German Research Foundation (Deutsche Forschungsgemeinschaft; grants to I.-T.K. and T.El.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Affiliations

Authors

Contributions

A.P., D.J.-F.d.Q., A.H., A.M. and M.F. conceived and designed the study. A.H., A.M., V.V., J.P., T.Eg., J.S., D.C., V.F., M.F., P.D., E.L., F.H., N.S., B.D.B., C.V., I.-T.K., S.W., T.El., D.J.-F.d.Q. and A.P. analysed the data. P.E., T.Se., T.Sc., C.B. and N.B. provided bioinformatic support. A.P., A.H. and D.J.-F.d.Q. wrote the manuscript. All authors reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Angela Heck or Andreas Papassotiropoulos.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Supplementary Information

Supplementary Tables 1–6, Supplementary Figures 1–6. (PDF 583 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Heck, A., Milnik, A., Vukojevic, V. et al. Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD. Nat Hum Behav 1, 0081 (2017). https://doi.org/10.1038/s41562-017-0081

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing