Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway
| Autor: | Nicodemus, Kk, Hargreaves, A, Morris, D, Anney, R, Gill, M, Corvin, A, Donohoe, G, Ripke, S, Sanders, Ar, Kendler, Ks, Levinson, Df, Sklar, P, Holmans, Pa, Lin, Dy, Duan, J, Ophoff, Ra, Andreassen, Oa, Scolnick, E, Cichon, S, Clair, St, D, Gurling, H, Werge, T, Rujescu, D, Blackwood, Dh, Pato, Cn, Malhotra, Ak, Purcell, S, Dudbridge, F, Neale, Bm, Rossin, L, Visscher, Pm, Posthuma, D, Ruderfer, Dm, Fanous, A, Stefansson, H, Steinberg, S, Mowry, Bj, Golimbet, V, Hert, De, M, Jönsson, Eg, Bitter, I, Pietiläinen, Op, Collier, Da, Tosato, Sarah, Agartz, I, Albus, M, Alexander, M, Amdur, Rl, Amin, F, Bass, N, Bergen, Se, Black, Dw, Børglum, Ad, Brown, Ma, Bruggeman, R, Buccola, Ng, Byerley, Wf, Cahn, W, Cantor, Rm, Carr, Vj, Catts, Sv, Choudhury, K, Cloninger, C, Cormican, P, Craddock, N, Danoy, Pa, Datta, S, Haan, De, L, Demontis, D, Dikeos, D, Djurovic, S, Donnelly, P, Duong, L, Dwyer, S, Fink Jensen, A, Freedman, R, Freimer, Nb, Friedl, M, Georgieva, L, Giegling, I, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, Am, Henskens, Fa, Hougaard, Dm, Hultman, Cm, Ingason, A, Jablensky, Av, Jakobsen, Kd, Jay, M, Jürgens, G, Kahn, Rs, Keller, Mc, Kenis, G, Kenny, E, Kim, Y, Kirov, Gk, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, Vk, Laurent, C, Lawrence, J, Lencz, T, Lerer, F, Liang, Ky, Lichtenstein, P, Lieberman, Ja, Linszen, Dh, Lönnqvist, J, Loughland, Cm, Maclean, Aw, Maher, Bs, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, Mcghee, Ka, Mcgrath, Jj, Mcintosh, A, Mclean, De, Mcquillin, A, Melle, I, Michie, Pt, Milanova, V, Morris, Dw, Mors, O, Mortensen, Pb, Moskvina, V, Muglia, P, Myin Germeys, I, Nertney, Da, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nöthen, Mm, O'Dushlaine, Ct, Olincy, A, Olsen, L, O'Neill, F, Ørntoft, Tf, Owen, Mj, Pantelis, C, Papadimitriou, G, Pato, Mt, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, Ae, Puri, V, Quested, D, Quinn, Em, Rasmussen, Hb, Réthelyi, Jm, Ribble, R, Rietschel, M, Riley, Bp, Ruggeri, Mirella, Schall, U, Schulze, Tg, Schwab, Sg, Scott, Rj, Shi, J, Sigurdsson, E, Silverman, Jm, Spencer, Cc, Stefansson, K, Strange, A, Strengman, E, Stroup, T, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, Jh, Timm, S, Toncheva, D, Van, Den, Oord, E, Van, Os, Van, J, Winkel, R, Veldink, J, Walsh, D, Wang, Ag, Wiersma, D, Wildenauer, Db, Williams, Hj, Williams, Nm, Wormley, B, Zammit, S, Sullivan, Pf, O'Donovan, Mc, Daly, Mj, Gejman, P. |
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| Přispěvatelé: | Functional Genomics, Complex Trait Genetics, De Hert, Marc, Myin-Germeys, Inez, van Winkel, Ruud, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Amsterdam Neuroscience, Adult Psychiatry |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
epistasis
Male Multifactorial Inheritance polygenic Neuropsychological Tests involvement 0302 clinical medicine Neural Pathways 2.1 Biological and endogenous factors Psychology schizophrenia risk psychosis variant Aetiology 0303 health sciences susceptibility gene znf804a medicine.diagnostic_test phenotypes Zinc Fingers Neuropsychological test Single Nucleotide Middle Aged Serious Mental Illness Psychiatry and Mental health Memory Short-Term Mental Health Schizophrenia Major depressive disorder Female Cognitive Sciences social and economic factors Adult medicine.medical_specialty Psychosis working memory schizophrenia IQ Schizoaffective disorder Polymorphism Single Nucleotide Article 03 medical and health sciences Gene interaction Genetic Social cognition Memory Clinical Research 2.3 Psychological Behavioral and Social Science medicine Genetics Humans Genetic Predisposition to Disease Bipolar disorder Polymorphism Psychiatry 030304 developmental biology Other Medical and Health Sciences Prevention Wellcome Trust Case Control Consortium 2 Neurosciences Genetic Variation Epistasis Genetic Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium medicine.disease attention Brain Disorders deficits Short-Term Psychotic Disorders genome-wide association Epistasis healthy controls identification Cognition Disorders 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Journal of the American Academy of Child and Adolescent Psychiatry, 71(7), 778-785. Elsevier Limited Nicodemus, K K, Hargreaves, A, Morris, D, Anney, R, Gill, M, Corvin, A, Donohoe, G & Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium 2014, ' Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway ', J A M A Psychiatry, vol. 71, no. 7, pp. 778-85 . https://doi.org/10.1001/jamapsychiatry.2014.528 JAMA psychiatry, vol 71, iss 7 Nicodemus, K K, Hargreaves, A, Morris, D, Anney, R, Gill, M, Corvin, A, Posthuma, D & Donohoe, G 2014, ' Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway. ', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 71, no. 7, pp. 778-785 . https://doi.org/10.1001/jamapsychiatry.2014.528 JAMA Psychiatry, 71(7), 778-785. American Medical Association JAMA psychiatry, 71(7), 778-785. American Medical Association |
| ISSN: | 2168-622X 0890-8567 2168-6238 |
| Popis: | IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424)were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition.We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1%to 3%of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2%using the polygenic score only to 4.8%(P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score. © 2014 American Medical Association. All rights reserved. |
| Databáze: | OpenAIRE |
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