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

Volumn 51, Issue , 2015, Pages 459-471

  Nievergelt, Caroline M ^a,c   Maihofer, Adam X ^a   Mustapic, Maja ^a   Yurgil, Kate A ^c   Schork, Nicholas J ^b   Miller, Mark W ^d,e   Logue, Mark W ^e,f   Geyer, Mark A ^a   Risbrough, Victoria B ^a,c   O'Connor, Daniel T ^a   Baker, Dewleen G ^a,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b J CRAIG VENTER INSTITUTE   (United States)

^c VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^d VA BOSTON HEALTHCARE SYSTEM   (United States)

^e BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Ancestry; Bipolar disorder; GWAS; GxE; Meta analysis; Pleiotropy; Polygenic risk score; PTSD; Trauma

Indexed keywords

GENOMIC DNA; PHOSPHORIBOSYLTRANSFERASE; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; PRTFDC1 PROTEIN, HUMAN;

ADULT; AFGHANISTAN; AFRICAN; AMERICAN INDIAN; ARTICLE; BIPOLAR DISORDER; CLUSTER ANALYSIS; CONTROLLED STUDY; DSM-IV; EUROPEAN; FEMALE; GENE; GENE INTERACTION; GENE LOCUS; GENE REPLICATION; GENETIC ASSOCIATION; GENOTYPE; HISPANIC; HUMAN; HUMAN GENOME; IMMUNE RESPONSE; IRAQ; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; MENTAL DISEASE; MILITARY DEPLOYMENT; NEUROPSYCHIATRY; POSTTRAUMATIC STRESS DISORDER; PREDICTION; PROSPECTIVE STUDY; PRTFDC1 GENE; PTSD GENE; RISK FACTOR; SCHIZOPHRENIA; SCORING SYSTEM; SINGLE NUCLEOTIDE POLYMORPHISM; SOLDIER; ADOLESCENT; COPING BEHAVIOR; GENETIC PREDISPOSITION; GENETICS; MIDDLE AGED; PSYCHOLOGY; YOUNG ADULT;

ADOLESCENT; ADULT; COMBAT DISORDERS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; MALE; MIDDLE AGED; MILITARY PERSONNEL; POLYMORPHISM, SINGLE NUCLEOTIDE; RESILIENCE, PSYCHOLOGICAL; STRESS DISORDERS, POST-TRAUMATIC; YOUNG ADULT;

EID: 84920626820     PISSN: 03064530     EISSN: 18733360     Source Type: Journal    
DOI: 10.1016/j.psyneuen.2014.10.017     Document Type: Article

References (68)

1. Almli L.M., et al. Genetic approaches to understanding post-traumatic stress disorder. Int. J. Neuropsychopharmacol. 2014, 17:355-370.
2. Amstadter A.B., et al. Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. J. Anxiety Disord. 2009, 23:369-373.
3. Amstadter A.B., et al. Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients. Dis. Markers 2011, 30:89-99.
4. Anderson C.A., et al. Data quality control in genetic case-control association studies. Nat. Protoc. 2010, 5:1564-1573.
5. APA Section 309.81: Posttraumatic Stress Disorder, Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR 2000, American Psychiatric Association, Washington, DC. fourth ed.
6. Baker D.G., et al. Predictors of risk and resilience for posttraumatic stress disorder among ground combat Marines: methods of the Marine Resiliency Study. Prev. Chronic. Dis. 2012, 9:E97.
7. Binder E.B., et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008, 299:1291-1305.
8. Boscarino J.A., et al. Association of FKBP5, COMT and CHRNA5 polymorphisms with PTSD among outpatients at risk for PTSD. Psychiatry Res. 2011, 188:173-174.
9. Bousman C.A., et al. Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2010, 153B:494-502.
10. Cao C., et al. Stathmin genotype is associated with reexperiencing symptoms of posttraumatic stress disorder in Chinese earthquake survivors. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013, 44:296-300.
11. Comings D.E., et al. Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication. Biol. Psychiatry 1996, 40:368-372.
12. Cross-Disorder Group of the Psychiatric Genomics Consortium, Genetic Risk Outcome of Psychosis Consortium Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013, 381:1371-1379.
13. Cross-Disorder Group of the Psychiatric Genomics Consortium Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 2013, 45:984-994.
14. Dragan W.L., Oniszczenko W. The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors. Anxiety Stress Coping 2009, 22:483-495.
15. Duncan L.E., Keller M.C. A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. Am. J. Psychiatry 2011, 168:1041-1049.
16. Falush D., et al. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 2003, 164:1567-1587.
17. Fu Q., et al. Differential etiology of posttraumatic stress disorder with conduct disorder and major depression in male veterans. Biol. Psychiatry 2007, 62:1088-1094.
18. Gillespie C.F., et al. Sex dependent influence of a functional polymorphism in steroid 5-alpha-reductase type 2 (SRD5A2) on post-traumatic stress symptoms. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2013, 162B:283-292.
19. Glatt S.J., et al. Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines: a pilot study. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2013, 162B:313-326.
20. Goenjian A.K., et al. Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms. J. Affect. Disord. 2012, 140:244-252.
21. Goenjian A.K., et al. Heritabilities of symptoms of posttraumatic stress disorder, anxiety, and depression in earthquake exposed Armenian families. Psychiatr. Genet. 2008, 18:261-266.
22. Grabe H.J., et al. Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. Am. J. Psychiatry 2009, 166:926-933.
23. 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 2013, 38:3029-3038.
24. Harrell F.E. rms: Regression Modeling Strategies. R Package Version 4.1-3 2014, http://cran.r-project.org/package=rms.
25. 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. 2011, 39:643-650.
26. Karam E.G., et al. The role of criterion A2 in the DSM-IV diagnosis of posttraumatic stress disorder. Biol. Psychiatry 2010, 68:465-473.
27. Keebaugh A.C., et al. Gene duplication and inactivation in the HPRT gene family. Genomics 2007, 89:134-142.
28. Kessler R.C., et al. Posttraumatic stress disorder in the National Comorbidity Survey. Arch. Gen. Psychiatry 1995, 52:1048-1060.
29. Kilpatrick D.G., et al. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J. Trauma. Stress 2013, 26:537-547.
30. Koenen K.C., et al. From candidate genes to genome-wide association: the challenges and promise of posttraumatic stress disorder genetic studies. Biol. Psychiatry 2013, 74:634-636.
31. Koenen K.C., et al. Gene-environment interaction in posttraumatic stress disorder: review, strategy and new directions for future research. Eur. Arch. Psychiatry Clin. Neurosci. 2008, 258:82-96.
32. Kolassa I.T., et al. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biol. Psychiatry 2010, 67:304-308.
33. Li J.Z., et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science 2008, 319:1100-1104.
34. 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 2013, 18:937-942.
35. Logue M.W., et al. The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity. Psychoneuroendocrinology 2013, 38:2249-2257.
36. Lyons M.J., et al. Gene-environment interaction of ApoE genotype and combat exposure on PTSD. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2013, 162B:762-769.
37. Mellman T.A., et al. Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population. Depress. Anxiety 2009, 26:993-997.
38. Nelson E.C., et al. Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults. Mol. Psychiatry 2009, 14:234-235.
39. Nievergelt C.M., et al. Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel. Investig. Genet. 2013, 4:13.
40. Nievergelt C.M., et al. Chip-based direct genotyping of coding variants in genome wide association studies: utility, issues and prospects. Gene 2014, 540:104-109.
41. Norrholm S.D., Ressler K.J. Genetics of anxiety and trauma-related disorders. Neuroscience 2009, 164:272-287.
42. Nugent N.R., et al. Genetics of post-traumatic stress disorder: informing clinical conceptualizations and promoting future research. Am. J. Med. Genet. C Semin. Med. Genet. 2008, 148:127-132.
43. Price A.L., et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 2006, 38:904-909.
44. Pritchard J.K., et al. Inference of population structure using multilocus genotype data. Genetics 2000, 155:945-959.
45. Pruim R.J., et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 2010, 26:2336-2337.
46. Purcell S., et al. Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003, 19:149-150.
47. Purcell S., et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 2007, 81:559-575.
48. Purcell S.M., et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009, 460:748-752.
49. Ressler K.J., et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 2011, 470:492-497.
50. Richardson L.K., et al. Prevalence estimates of combat-related post-traumatic stress disorder: critical review. Aust. N.Z. J. Psychiatry 2010, 44:4-19.
51. Roberts A.L., et al. Race/ethnic differences in exposure to traumatic events, development of post-traumatic stress disorder, and treatment-seeking for post-traumatic stress disorder in the United States. Psychol. Med. 2010, 1-13.
52. Sartor C.E., et al. Common heritable contributions to low-risk trauma, high-risk trauma, posttraumatic stress disorder, and major depression. Arch. Gen. Psychiatry 2012, 69:293-299.
53. Schizophrenia Psychiatric Genome-Wide Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 2011, 43:969-976.
54. Segman R.H., et al. Association between the dopamine transporter gene and posttraumatic stress disorder. Mol. Psychiatry 2002, 7:903-907.
55. Solovieff N., et al. Pleiotropy in complex traits: challenges and strategies. Nat. Rev. Genet. 2013, 14:483-495.
56. Solovieff N., et al. Genetic association analysis of 300 genes identifies a risk haplotype in SLC18A2 for post-traumatic stress disorder in two independent samples. Neuropsychopharmacology 2014, 39:1872-1879.
57. Sullivan P.F. Spurious genetic associations. Biol. Psychiatry 2007, 61:1121-1126.
58. Suzuki E., et al. PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation. Oncogene 2007, 26:7921-7932.
59. Voisey J., et al. A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia. Behav. Brain Funct. 2010, 6:41.
60. Voorman A., et al. Behavior of QQ-plots and genomic control in studies of gene-environment interaction. PLoS ONE 2011, 6:e19416.
61. Wilker S., et al. The role of memory-related gene WWC1 (KIBRA) in lifetime posttraumatic stress disorder: evidence from two independent samples from African conflict regions. Biol. Psychiatry 2013, 74:664-671.
62. Willer C.J., et al. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 2010, 26:2190-2191.
63. Wolf E.J., et al. Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder. Psychol. Med. 2013, 1-11.
64. Xian H., et al. Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs. Drug Alcohol Depend. 2000, 61:95-102.
65. Xie P., et al. Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Arch. Gen. Psychiatry 2009, 66:1201-1209.
66. Xie P., et al. Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder. Biol. Psychiatry 2013, 74:656-663.
67. Yurgil K.A., et al. Association between traumatic brain injury and risk of posttraumatic stress disorder in active-duty marines. JAMA psychiatry 2014, 71:149-157.
68. Zoladz P.R., Diamond D.M. Current status on behavioral and biological markers of PTSD: a search for clarity in a conflicting literature. Neurosci. Biobehav. Rev. 2013, 37:860-895.