The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity

Psychoneuroendocrinology

Volumn 38, Issue 10, 2013, Pages 2249-2257

  Logue, Mark W ^a,b   Solovieff, Nadia ^c,d,e   Leussis, Melanie P ^c,e,g   Wolf, Erika J ^a,f   Melista, Efthymia ^a   Baldwin, Clinton ^a   Koenen, Karestan C ^h   Petryshen, Tracey L ^c,d,e   Miller, Mark W ^a,f  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

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

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^f VA BOSTON HEALTHCARE SYSTEM   (United States)

^g EMMANUEL COLLEGE   (United States)

^h Columbia University ^*  (United States)

Author keywords

ANK3; Candidate gene; Externalizing; Genetic association; Posttraumatic stress disorder

Indexed keywords

ADULT; AGED; ANKYRIN 3 GENE; ANTISOCIAL PERSONALITY DISORDER; ARTICLE; BIPOLAR DISORDER; CAUCASIAN; COHORT ANALYSIS; COMORBIDITY; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC RISK; HUMAN; IMPULSIVENESS; MAJOR CLINICAL STUDY; MALE; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; REGULATOR GENE; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM; SUBSTANCE ABUSE; TEMPERAMENT; VETERAN;

ANK3; CANDIDATE GENE; EXTERNALIZING; GENETIC ASSOCIATION; POSTTRAUMATIC STRESS DISORDER;

ADULT; AGED; ANKYRINS; COMORBIDITY; EXPRESSED EMOTION; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MENTAL DISORDERS; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; STRESS DISORDERS, POST-TRAUMATIC; VETERANS; YOUNG ADULT;

EID: 84883878873     PISSN: 03064530     EISSN: 18733360     Source Type: Journal    
DOI: 10.1016/j.psyneuen.2013.04.013     Document Type: Article

References (39)

1. Adzhubei I.A., Schmidt S., Peshkin L., Ramensky V.E., Gerasimova A., Bork P., Kondrashov A.S., Sunyaev S.R. A method and server for predicting damaging missense mutations. Nat. Methods 2010, 7:248-249.
2. Athanasiu L., Mattingsdal M., Kahler A.K., Brown A., Gustafsson O., Agartz I., Giegling I., Muglia P., Cichon S., Rietschel M., Pietilainen O.P., Peltonen L., Bramon E., Collier D., Clair D.S., Sigurdsson E., Petursson H., Rujescu D., Melle I., Steen V.M., Djurovic S., Andreassen O.A. Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. J. Psychiatr. Res. 2010, 44:748-753.
3. Barrett J.C., Fry B., Maller J., Daly M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21:263-265.
4. Baum A.E., Akula N., Cabanero M., Cardona I., Corona W., Klemens B., Schulze T.G., Cichon S., Rietschel M., Nothen M.M., Georgi A., Schumacher J., Schwarz M., Abou Jamra R., Hofels S., Propping P., Satagopan J., Detera-Wadleigh S.D., Hardy J., McMahon F.J. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol. Psychiatry 2008, 13:197-207.
5. Blake D.D., Weathers F.W., Nagy L.M., Kaloupek D.G., Charney D.S., Keane T.M. The Clinician-Administered PTSD Scale-IV 1990, National Center for Posttraumatic Stress Disorder, Behavioral Sciences Division, Boston.
6. Blake D.D., Weathers F.W., Nagy L.M., Kaloupek D.G., Gusman F.D., Charney D.S., Keane T.M. The development of a Clinician-Administered PTSD Scale. J. Trauma. Stress 1995, 8:75-90.
7. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013, 381:1371-1379. Cross-Disorder Group of the Psychiatric Genomics Consortium.
8. Falush D., Stephens M., Pritchard J.K. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 2003, 164:1567-1587.
9. Ferreira M.A., O'Donovan M.C., Meng Y.A., Jones I.R., Ruderfer D.M., Jones L., Fan J., Kirov G., Perlis R.H., Green E.K., Smoller J.W., Grozeva D., Stone J., Nikolov I., Chambert K., Hamshere M.L., Nimgaonkar V.L., Moskvina V., Thase M.E., Caesar S., Sachs G.S., Franklin J., Gordon-Smith K., Ardlie K.G., Gabriel S.B., Fraser C., Blumenstiel B., Defelice M., Breen G., Gill M., Morris D.W., Elkin A., Muir W.J., McGhee K.A., Williamson R., Macintyre D.J., Maclean A.W., St Clair D., Robinson M., Van Beck M., Pereira A.C., Kandaswamy R., McQuillin A., Collier D.A., Bass N.J., Young A.H., Lawrence J., Nicol Ferrier I., Anjorin A., Farmer A., Curtis D., Scolnick E.M., McGuffin P., Daly M.J., Corvin A.P., Holmans P.A., Blackwood D.H., Gurling H.M., Owen M.J., Purcell S.M., Sklar P., Craddock N. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat. Genet. 2008, 17:17.
10. First M.B., Spitzer R.L., Gibbon M., Williams J. Structured Clinical Interview for Axis I DSM-IV Disorders 1994, Biometrics Research, New York.
11. First M.B., Spitzer R.L., Gibbon M., Williams J.B.W. The Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II). Part I. Description. J. Personal. Disord. 1995, 9:83-91.
12. Fruhholz S., Ceravolo L., Grandjean D. Specific brain networks during explicit and implicit decoding of emotional prosody. Cereb. Cortex 2012, 22:1107-1117.
13. James L.M., Engdahl B.E., Leuthold A.C., Lewis S.M., Van Kampen E., Georgopoulos A.P. Neural network modulation by trauma as a marker of resilience: differences between veterans with posttraumatic stress disorder and resilient controls. JAMA Psychiatry 2013, 1-9.
14. Krueger R.F., South S.C. Externalizing disorders: cluster 5 of the proposed meta-structure for DSM-V and ICD-11. Psychol. Med. 2009, 39:2061-2070.
15. Leussis M.P., Berry-Scott E.M., Saito M., Jhuang H., de Haan G., Alkan O., Luce C.J., Madison J.M., Sklar P., Serre T., Root D.E., Petryshen T.L. The ankyrin 3 (ANK3) bipolar disorder gene regulates mood-related behaviors that are modulated by lithium and stress. Biol. Psychiatry 2012, 73:683-690.
16. Leussis M.P., Madison J.M., Petryshen T.L. Ankyrin 3: genetic association with bipolar disorder and relevance to disease pathophysiology. Biol Mood Anxiety Disord 2012, 2:18.
17. Liang K.Y., Zeger S.L. Longitudinal data analysis using linear models. Biometrika 1986, 73:13-22.
18. Logue M.W., Baldwin C., Guffanti G., Melista E., Wolf E.J., Reardon A.F., Uddin M., Wildman D., Galea S., Koenen K.C., Miller M.W. 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 2012, [Epub ahead of print].
19. Loranger A. International Personality Disorder Examination: DSM-IV and ICD-10 Interviews 1999, Psychological Assessment Resources, Inc., Lutz, FL.
20. Miller M.W., Kaloupek D.G., Dillon A.L., Keane T.M. Externalizing and internalizing subtypes of combat-related PTSD: a replication and extension using the PSY-5 scales. J. Abnorm. Psychol. 2004, 113:636-645.
21. Park J.Y., Gu B.M., Kang D.H., Shin Y.W., Choi C.H., Lee J.M., Kwon J.S. Integration of cross-modal emotional information in the human brain: an fMRI study. Cortex; A Journal Devoted to the Study of the Nervous System and Behavior 2010, 46:161-169.
22. Patrick C.J., Venables N.C., Yancey J.R., Hicks B.M., Nelson L.D., Kramer M.D. A construct-network approach to bridging diagnostic and physiological domains: application to assessment of externalizing psychopathology. J. Abnorm. Psychol. 2013, (in press).
23. Price A.L., Patterson N.J., Plenge R.M., Weinblatt M.E., Shadick N.A., Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 2006, 38:904-909. (Epub 2006 July 2023).
24. Pritchard J.K., Stephens M., Donnelly P. Inference of population structure using multilocus genotype data. Genetics 2000, 155:945-959.
25. Purcell S., Neale B., Todd-Brown K., Thomas L., Ferreira M.A., Bender D., Maller J., Sklar P., de Bakker P.I., Daly M.J., Sham P.C. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 2007, 81:559-575. (Epub 2007 July 2025).
26. R Development Core Team R: A Language and Environment for Statistical Computing 2008.
27. Ripke S., Sanders A.R., Kendler K.S., Levinson D.F., Sklar P., Holmans P.A., Lin D.Y., Duan J., Ophoff R.A., Andreassen O.A., Scolnick E., Cichon S., St Clair D., Corvin A., Gurling H., Werge T., Rujescu D., Blackwood D.H., Pato C.N., Malhotra A.K., Purcell S., Dudbridge F., Neale B.M., Rossin L., Visscher P.M., Posthuma D., Ruderfer D.M., Fanous A., Stefansson H., Steinberg S., Mowry B.J., Golimbet V., De Hert M., Jonsson E.G., Bitter I., Pietilainen O.P., Collier D.A., Tosato S., Agartz I., Albus M., Alexander M., Amdur R.L., Amin F., Bass N., Bergen S.E., Black D.W., Borglum A.D., Brown M.A., Bruggeman R., Buccola N.G., Byerley W.F., Cahn W., Cantor R.M., Carr V.J., Catts S.V., Choudhury K., Cloninger C.R., Cormican P., Craddock N., Danoy P.A., Datta S., de Haan L., Demontis D., Dikeos D., Djurovic S., Donnelly P., Donohoe G., Duong L., Dwyer S., Fink-Jensen A., Freedman R., Freimer N.B., Friedl M., Georgieva L., Giegling I., Gill M., Glenthoj B., Godard S., Hamshere M., Hansen M., Hansen T., Hartmann A.M., Henskens F.A., Hougaard D.M., Hultman C.M., Ingason A., Jablensky A.V., Jakobsen K.D., Jay M., Jurgens G., Kahn R.S., Keller M.C., Kenis G., Kenny E., Kim Y., Kirov G.K., Konnerth H., Konte B., Krabbendam L., Krasucki R., Lasseter V.K., Laurent C., Lawrence J., Lencz T., Lerer F.B., Liang K.Y., Lichtenstein P., Lieberman J.A., Linszen D.H., Lonnqvist J., Loughland C.M., Maclean A.W., Maher B.S., Maier W., Mallet J., Malloy P., Mattheisen M., Mattingsdal M., McGhee K.A., McGrath J.J., McIntosh A., McLean D.E., McQuillin A., Melle I., Michie P.T., Milanova V., Morris D.W., Mors O., Mortensen P.B., Moskvina V., Muglia P., Myin-Germeys I., Nertney D.A., Nestadt G., Nielsen J., Nikolov I., Nordentoft M., Norton N., Nothen M.M., O'Dushlaine C.T., Olincy A., Olsen L., O'Neill F.A., Orntoft T.F., Owen M.J., Pantelis C., Papadimitriou G., Pato M.T., Peltonen L., Petursson H., Pickard B., Pimm J., Pulver A.E., Puri V., Quested D., Quinn E.M., Rasmussen H.B., Rethelyi J.M., Ribble R., Rietschel M., Riley B.P., Ruggeri M., Schall U., Schulze T.G., Schwab S.G., Scott R.J., Shi J., Sigurdsson E., Silverman J.M., Spencer C.C., Stefansson K., Strange A., Strengman E., Stroup T.S., Suvisaari J., Terenius L., Thirumalai S., Thygesen J.H., Timm S., Toncheva D., van den Oord E., van Os J., van Winkel R., Veldink J., Walsh D., Wang A.G., Wiersma D., Wildenauer D.B., Williams H.J., Williams N.M., Wormley B., Zammit S., Sullivan P.F., O'Donovan M.C., Daly M.J., Gejman P.V. Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 2011, 43:969-976.
28. Robins D.L., Hunyadi E., Schultz R.T. Superior temporal activation in response to dynamic audio-visual emotional cues. Brain Cogn. 2009, 69:269-278.
29. Roussos P., Giakoumaki S.G., Georgakopoulos A., Robakis N.K., Bitsios P. The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males. Bipolar Disord. 2011, 13:250-259.
30. Roussos P., Katsel P., Davis K.L., Bitsios P., Giakoumaki S.G., Jogia J., Rozsnyai K., Collier D., Frangou S., Siever L.J., Haroutunian V. Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia. Arch. Gen. Psychiatry 2012, 69:7-15.
31. Rueckert E.H., Barker D., Ruderfer D., Bergen S.E., O'Dushlaine C., Luce C.J., Sheridan S.D., Theriault K.M., Chambert K., Moran J., Purcell S.M., Madison J.M., Haggarty S.J., Sklar P. Cis-acting regulation of brain-specific ANK3 gene expression by a genetic variant associated with bipolar disorder. Mol. Psychiatry 2012, [Epub ahead of print].
32. Schulze T.G., Detera-Wadleigh S.D., Akula N., Gupta A., Kassem L., Steele J., Pearl J., Strohmaier J., Breuer R., Schwarz M., Propping P., Nothen M.M., Cichon S., Schumacher J., Rietschel M., McMahon F.J. Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder. Mol. Psychiatry 2009, 14:487-491.
33. Scott L.J., Muglia P., Kong X.Q., Guan W., Flickinger M., Upmanyu R., Tozzi F., Li J.Z., Burmeister M., Absher D., Thompson R.C., Francks C., Meng F., Antoniades A., Southwick A.M., Schatzberg A.F., Bunney W.E., Barchas J.D., Jones E.G., Day R., Matthews K., McGuffin P., Strauss J.S., Kennedy J.L., Middleton L., Roses A.D., Watson S.J., Vincent J.B., Myers R.M., Farmer A.E., Akil H., Burns D.K., Boehnke M. Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:7501-7506.
34. Sklar P., Ripke S., Scott L.J., Andreassen O.A., Cichon S., Craddock N., Edenberg H.J., Nurnberger J.I., Rietschel M., Blackwood D., Corvin A., Flickinger M., Guan W., Mattingsdal M., McQuillin A., Kwan P., Wienker T.F., Daly M., Dudbridge F., Holmans P.A., Lin D., Burmeister M., Greenwood T.A., Hamshere M.L., Muglia P., Smith E.N., Zandi P.P., Nievergelt C.M., McKinney R., Shilling P.D., Schork N.J., Bloss C.S., Foroud T., Koller D.L., Gershon E.S., Liu C., Badner J.A., Scheftner W.A., Lawson W.B., Nwulia E.A., Hipolito M., Coryell W., Rice J., Byerley W., McMahon F.J., Schulze T.G., Berrettini W., Lohoff F.W., Potash J.B., Mahon P.B., McInnis M.G., Zollner S., Zhang P., Craig D.W., Szelinger S., Barrett T.B., Breuer R., Meier S., Strohmaier J., Witt S.H., Tozzi F., Farmer A., McGuffin P., Strauss J., Xu W., Kennedy J.L., Vincent J.B., Matthews K., Day R., Ferreira M.A., O'Dushlaine C., Perlis R., Raychaudhuri S., Ruderfer D., Hyoun P.L., Smoller J.W., Li J., Absher D., Thompson R.C., Meng F.G., Schatzberg A.F., Bunney W.E., Barchas J.D., Jones E.G., Watson S.J., Myers R.M., Akil H., Boehnke M., Chambert K., Moran J., Scolnick E., Djurovic S., Melle I., Morken G., Gill M., Morris D., Quinn E., Muhleisen T.W., Degenhardt F.A., Mattheisen M., Schumacher J., Maier W., Steffens M., Propping P., Nothen M.M., Anjorin A., Bass N., Gurling H., Kandaswamy R., Lawrence J., McGhee K., McIntosh A., McLean A.W., Muir W.J., Pickard B.S., Breen G., St Clair D., Caesar S., Gordon-Smith K., Jones L., Fraser C., Green E.K., Grozeva D., Jones I.R., Kirov G., Moskvina V., Nikolov I., O'Donovan M.C., Owen M.J., Collier D.A., Elkin A., Williamson R., Young A.H., Ferrier I.N., Stefansson K., Stefansson H., Thornorgeirsson T., Steinberg S., Gustafsson O., Bergen S.E., Nimgaonkar V., Hultman C., Landen M., Lichtenstein P., Sullivan P., Schalling M., Osby U., Backlund L., Frisen L., Langstrom N., Jamain S., Leboyer M., Etain B., Bellivier F., Petursson H., Sigur Sson E., Muller-Mysok B., Lucae S., Schwarz M., Schofield P.R., Martin N., Montgomery G.W., Lathrop M., Oskarsson H., Bauer M., Wright A., Mitchell P.B., Hautzinger M., Reif A., Kelsoe J.R., Purcell S.M. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat. Genet. 2011, 43:977-983.
35. Smith E.N., Bloss C.S., Badner J.A., Barrett T., Belmonte P.L., Berrettini W., Byerley W., Coryell W., Craig D., Edenberg H.J., Eskin E., Foroud T., Gershon E., Greenwood T.A., Hipolito M., Koller D.L., Lawson W.B., Liu C., Lohoff F., McInnis M.G., McMahon F.J., Mirel D.B., Murray S.S., Nievergelt C., Nurnberger J., Nwulia E.A., Paschall J., Potash J.B., Rice J., Schulze T.G., Scheftner W., Panganiban C., Zaitlen N., Zandi P.P., Zollner S., Schork N.J., Kelsoe J.R. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol. Psychiatry 2009, 14:755-763.
36. Tesli M., Koefoed P., Athanasiu L., Mattingsdal M., Gustafsson O., Agartz I., Rimol L.M., Brown A., Wirgenes K.V., Smorr L.L., Kahler A.K., Werge T., Mors O., Mellerup E., Jonsson E.G., Melle I., Morken G., Djurovic S., Andreassen O.A. Association analysis of ANK3 gene variants in nordic bipolar disorder and schizophrenia case-control samples. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics 2011, 156B:969-974.
37. Wolf E.J., Miller M.W., Krueger R.F., Lyons M.J., Tsuang M.T., Koenen K.C. Posttraumatic stress disorder and the genetic structure of comorbidity. J. Abnorm. Psychol. 2010, 119:320-330.
38. Zeger S.L., Liang K.Y. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986, 42:121-130.
39. Zhou D., Lambert S., Malen P.L., Carpenter S., Boland L.M., Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J. Cell Biol. 1998, 143:1295-1304.