The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance.
OCD
PRS
harm avoidance
obsessive-compulsive disorder
polygenic risk score
Journal
Acta psychiatrica Scandinavica
ISSN: 1600-0447
Titre abrégé: Acta Psychiatr Scand
Pays: United States
ID NLM: 0370364
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
accepted:
09
08
2020
pubmed:
14
8
2020
medline:
19
8
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
326-336Informations de copyright
© 2020 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.
Références
Weissman MM, Bland RC, Canino GJ et al. The cross national epidemiology of obsessive-compulsive disorder. J Clin Psychiatry2020;55(3 Suppl.):5-10.
Grabe HJ, Ruhrmann S, Ettelt S et al. Familiality of obsessive-compulsive disorder in nonclinical and clinical subjects. Am J Psychiatry 2006;163:1986-1992.
Nestadt G, Samuels J, Riddle M et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57:358-363.
Pauls DL, Alsobrook JP II, Goodman W et al. A family study of obsessive-compulsive disorder. Am J Psychiatry 1995;152:76-84.
Mataix-Cols D, Boman M, Monzani B et al. Population-based, multigenerational family clustering study of obsessive-compulsive disorder. JAMA Psychiatry 2013;70:709-717.
Nicolini H, Arnold P, Nestadt G et al. Overview of genetics and obsessive-compulsive disorder. Psychiatry Res 2009;170:7-14.
Van Grootheest DS, Bartels M, Van Beijsterveldt CE et al. Genetic and environmental contributions to self-report obsessive-compulsive symptoms in Dutch adolescents at ages 12, 14, and 16. J Am Acad Child Adolesc Psychiatry 2008;47:1182-1188.
Cappi C, Brentani H, Lima L et al. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways. Transl Psychiatry 2016;6:e764.
Cappi C, Oliphant ME, Péter Z et al. De novo damaging DNA coding mutations are associated with obsessive-compulsive disorder and overlap with tourette’s disorder and autism. Biol Psychiatry 2019;87:1035-1044.
Halvorsen M, Samuels JF, Wang Y et al. Rare and de novo variants in obsessive compulsive disorder. Eur Neuropsychopharmacol 2019;29:S860-S861.
Guo W, Samuels JF, Wang Y et al. Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD. Eur Neuropsychopharmacol 2017;27:657-666.
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS). Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis. Mol Psychiatry 2018;23:1181.
Mattheisen M, Samuels JF, Wang Y et al. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 2015;20:337-344.
Stewart SE, Yu D, Scharf JM et al. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry 2013;18:788-798.
Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636-645.
Iacono WG, Malone SM, Vrieze SI. Endophenotype best practices. Int J Psychophysiol 2017;111:115-144.
Cloninger CR, Svrakic DM. Integrative psychobiological approach to psychiatric assessment and treatment. Psychiatry 1997;60:120-141.
Garcia D, Lundström S, Brändström S et al. Temperament and Character in the Child and Adolescent Twin Study in Sweden (CATSS): comparison to the general population, and genetic structure analysis. PLoS One 2013;8:e70475.
Gillespie NA, Cloninger CR, Heath AC et al. The genetic and environmental relationship between Cloninger's dimensions of temperament and character. Pers Individ Dif 2003;35:1931-1946.
Keller MC, Coventry WL, Heath AC et al. Widespread evidence for non-additive genetic variation in Cloninger’s and Eysenck’s personality dimensions using a twin plus sibling design. Behav Genet 2005;35:707-721.
Josefsson K, Jokela M, Cloninger CR et al. Maturity and change in personality: developmental trends of temperament and character in adulthood. Dev Psychopathol 2013;25:713-727.
Fossey MD, Roy-Byrne PP, Cowley DS et al. Personality assessment using the Tridimensional Personality Questionnaire (TPQ) in patients with panic disorder and generalized anxiety disorder. Biol Psychiatry 1989;25:10-13.
Kim SJ, Kang JI, Kim CH. Temperament and character in subjects with obsessive-compulsive disorder. Compr Psychiatry 2009;50:567-572.
Richter MA, Summerfeldt LJ, Joffe RT et al. The Tridimensional Personality Questionnaire in obsessive-compulsive disorder. Psychiatry Res 1996;65:185-188.
Summerfeldt LJ, Kloosterman PH, Antony MM, Swinson RP. Examining an obsessive-compulsive core dimensions model: Structural validity of harm avoidance and incompleteness. J Obsessive Compuls Relat Disord 2014;3:83-94.
Bey K, Lennertz L, Riesel A et al. Harm avoidance and childhood adversities in patients with obsessive-compulsive disorder and their unaffected first-degree relatives. Acta Psychiatr Scand 2017;135:328-338.
Calvo R, Lázaro L, Castro-Fornieles J et al. Obsessive-compulsive personality disorder traits and personality dimensions in parents of children with obsessive-compulsive disorder. Eur Psychiatry 2009;24:201-206.
Ettelt S, Grabe HJ, Ruhrmann S et al. Harm avoidance in subjects with obsessive-compulsive disorder and their families. J Affect Disord 2008;107:265-269.
International Schizophrenia Consortium, Purcell SM, Wray NR et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009;460:748-752.
Burton CL, Wright L, Shan J et al. SWAN scale for ADHD trait-based genetic research: a validity and polygenic risk study. J Child Psychol Psychiatry 2019;60:988-997.
Liu M, Malone SM, Vaidyanathan U et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychol Med 2017;47:1116-1125.
Ranlund S, Calafato S, Thygesen JH et al. A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains. Am J Medical Genet B Neuropsychiatr Genet 2018;177:21-34.
Wang SH, Hsiao PC, Yeh LL et al. Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia. Genes Brain Behav 2018;17:49-55.
Yüksel D, Dietsche B, Forstner AJ et al. Polygenic risk for depression and the neural correlates of working memory in healthy subjects. Prog Neuropsychopharmacol Biol Psychiatry 2017;79:67-76.
Taylor MJ, Martin J, Lu Y et al. Association of genetic risk factors for psychiatric disorders and traits of these disorders in a Swedish population twin sample. JAMA Psychiatry 2019;76:280-289.
Den Braber A, Zilhao NR, Fedko IO et al. Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs. Transl Psychiatry 2016;6:e731.
Bey K, Lennertz L, Grützmann R et al. Impaired antisaccades in obsessive-compulsive disorder: Evidence from meta-analysis and a large empirical study. Front Psychiatry 2018;9:284.
First MB, Spitzer RL, Gibbon M et al. User's guide for the Structured Clinical Interview for DSM-IV axis I Disorders SCID-I: clinician version. Arlington: American Psychiatric Association Publishing; 1997.
Wittchen HU, Zaudig M, Fydrich T. SKID. Strukturiertes klinisches Interview für DSM-IV. Achse I und II. Handanweisung [Structured Clinical Interview for DSM-IV. Axis I and II. Manual]. Göttingen, Germany: Hogrefe; 1997.
Cloninger CR, Przybeck TR, Svrakic DM et al. The Temperament and Character Inventory (TCI): A guide to its development and use. Washington: Center for Psychobiology of Personality; 1994.
Richter J, Eisemann M, Richter G. German version of the temperament and character inventory. Zeitschrift für Klinische Psychologie-Forschung und Praxis 2000;29:117-126.
Goodman WK, Price LH, Rasmussen SA et al. The Yale brown obsessive compulsive scale: II. Validity. Arch Gen Psychiatry 1989;46:1012-1016.
Hand I, Büttner-Westphal H. Die Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Ein halbstrukturiertes Interview zur Beurteilung des Schweregrades von Denk-und Handlungszwängen. Verhaltenstherapie 1991;1:223-225.
Foa EB, Huppert JD, Leiberg S et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002;14:485-496.
Gönner S, Leonhart R, Ecker W. The obsessive-compulsive inventory-revised (OCI-R): validation of the German version in a sample of patients with OCD, anxiety disorders, and depressive disorders. J Anxiety Disord 2008;22:734-749.
Cervin M, Perrin S, Olsson E et al. Incompleteness, harm avoidance, and disgust: a comparison of youth with OCD, anxiety disorders, and no psychiatric disorder. J Anxiety Disord 2020;69:102175.
Ecker W, Gönner S. Incompleteness and harm avoidance in OCD symptom dimensions. Behav Res Ther 2008;46:895-904.
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS); 2018; OCD_Aug2017; Retrieved from https://www.med.unc.edu/pgc/download-results/ocd/
Purcell S, Neale B, Todd-Brown K et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559-575.
Choi SW, Mak TSH, O'Reilly P. A guide to performing Polygenic Risk Score analyses. BioRxiv 2018. https://doi.org/10.1101/416545.
Hayes AF. Introduction to mediation, moderation, and conditional process analysis: A regression-based approach. New York: Guilford Publications; 2017.
Hayes AF, Cai L. Using heteroskedasticity-consistent standard error estimators in OLS regression: An introduction and software implementation. Behav Res Methods 2007;39:709-722.
Taylor S. Early versus late onset obsessive-compulsive disorder: evidence for distinct subtypes. Clin Psychol Rev 2011;31:1083-1100.
Brainstorm Consortium, Anttila V, Bulik-Sullivan B et al. Analysis of shared heritability in common disorders of the brain. Science 2018;360:eaap8757.
Aluja A, Blanch A. The five and seven factors personality models: differences and similitude between the TCI-R, NEO-FFI-R and ZKPQ-50-CC. Span J Psychol 2011;14:659-666.
Service SK, Verweij KJH, Lahti J et al. A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales. Transl Psychiatry 2012;2:e116.
Verweij KJ, Zietsch BP, Medland SE et al. A genome-wide association study of Cloninger's temperament scales: implications for the evolutionary genetics of personality. Biol Psychol 2010;85:306-317.
Wang KS, Liu X, Aragam N et al. Polymorphisms in ABLIM1 are associated with personality traits and alcohol dependence. J Mol Neurosci 2012;46:265-271.
Lyoo IK, Yoon T, Kang DH et al. Patterns of changes in temperament and character inventory scales in subjects with obsessive-compulsive disorder following a 4-month treatment. Acta Psychiatr Scand 2003;107:298-304.
Cuthbert BN, Insel TR. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med 2013;11:126.
Beucke JC, Sepulcre J, Eldaief MC et al. Default mode network subsystem alterations in obsessive-compulsive disorder. Br J Psychiatry 2014;205:376-382.
Gürsel DA, Avram M, Sorg C et al. Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: a meta-analysis of resting-state functional connectivity. Neurosci Biobehav Rev 2018;87:151-160.
Huggins AA, Belleau EL, Miskovich TA et al. Moderating effects of harm avoidance on resting-state functional connectivity of the anterior insula. Front Hum Neurosci 2018;12:447.
Jiang R, Calhoun VD, Zuo N et al. Connectome-based individualized prediction of temperament trait scores. NeuroImage 2018;183:366-374.
Riesel A. The erring brain: Error-related negativity as an endophenotype for OCD-A review and meta-analysis. Psychophysiology 2019;56:e13348.
Riesel A, Klawohn J, Grützmann R et al. Error-related brain activity as a transdiagnostic endophenotype for obsessive-compulsive disorder, anxiety and substance use disorder. Psychol Med 2019;49:1207-1217.
Hasler G, LaSalle-Ricci VH, Ronquillo JG et al. Obsessive-compulsive disorder symptom dimensions show specific relationships to psychiatric comorbidity. Psychiatry Res 2005;135:121-132.
López-Solà C, Fontenelle LF, Verhulst B et al. Distinct etiological influences on obsessive-compulsive symptom dimensions: A multivariate twin study. Depress Anxiety 2016;33:179-191.
Taj MJRJ, Ganesh S, Shukla T et al. BDNF gene and obsessive compulsive disorder risk, symptom dimensions and treatment response. Asian J Psychiatry 2017;38:65-69.
Viswanath B, Purushottam M, Kandavel T et al. DRD4 gene and obsessive compulsive disorder: do symptom dimensions have specific genetic correlates? Prog Neuropsychopharmacol Biol Psychiatry 2013;41:18-23.
Alemany-Navarro M, Cruz R, Real E et al. Looking into the genetic bases of OCD dimensions: a pilot genome-wide association study. Transl Psychiatry 2020;10:1-16.
Pauls DL, Abramovitch A, Rauch SL et al. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci 2014;15:410-424.
Alemany-Navarro M, Costas J, Real E et al. Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene-environment interaction approach. Transl Psychiatry 2019;9:70.
Miller GA, Chapman JP. Misunderstanding analysis of covariance. J Abnorm Psychol 2001;110:40.
Kampman O, Viikki M, Järventausta K et al. Meta-analysis of anxiety disorders and temperament. Neuropsychobiology 2014;69:175-186.