Hostname: page-component-594f858ff7-x2rdm Total loading time: 0 Render date: 2023-06-10T08:59:27.544Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "corePageComponentUseShareaholicInsteadOfAddThis": true, "coreDisableSocialShare": false, "useRatesEcommerce": true } hasContentIssue false
  • English

Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study

Published online by Cambridge University Press:  15 August 2019

Jim van Os Open the ORCID record for Jim van Os[Opens in a new window] ,
Lotta-Katrin Pries ,
Philippe Delespaul ,
Gunter Kenis ,
Jurjen J. Luykx ,
Bochao D. Lin ,
Alexander L. Richards ,
Berna Akdede ,
Tolga Binbay  and
Vesile Altınyazar
...Show all authors
Jim van Os*
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, London, UK
Lotta-Katrin Pries
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
Philippe Delespaul
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
Gunter Kenis
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
Jurjen J. Luykx
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Bochao D. Lin
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Alexander L. Richards
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK
Berna Akdede
Affiliation:
Department of Psychiatry, Dokuz Eylul University School of Medicine, Izmir, Turkey
Tolga Binbay
Affiliation:
Department of Psychiatry, Dokuz Eylul University School of Medicine, Izmir, Turkey
Vesile Altınyazar
Affiliation:
Department of Psychiatry, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey
Berna Yalınçetin
Affiliation:
Department of Neuroscience, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey
Güvem Gümüş-Akay
Affiliation:
Ankara University Brain Research Center, Ankara, Turkey
Burçin Cihan
Affiliation:
Department of Psychology, Middle East Technical University, Çankaya, Ankara, Turkey
Haldun Soygür
Affiliation:
Department of Psychiatry, School of Medicine, Dokuz Eylül University (discharged by decree 701 on July 8, 2018 because of signing “Peace Petition”)
Halis Ulaş
Affiliation:
Department of Psychiatry, School of Medicine, Dokuz Eylül University (discharged by decree 701 on July 8, 2018 because of signing “Peace Petition”)
Eylem Şahin Cankurtaran
Affiliation:
Güven Çayyolu Healthcare Campus, Ankara, Turkey
Semra Ulusoy Kaymak
Affiliation:
Atatürk Research and Training Hospital Psychiatry Clinic, Ankara, Turkey
Marina M. Mihaljevic
Affiliation:
Faculty of Medicine, University of Belgrade, Belgrade, Serbia Clinic for Psychiatry CCS, Belgrade, Serbia
Sanja Andric Petrovic
Affiliation:
Clinic for Psychiatry CCS, Belgrade, Serbia
Tijana Mirjanic
Affiliation:
Special Hospital for Psychiatric Disorders Kovin, Kovin, Serbia
Miguel Bernardo
Affiliation:
Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain
Bibiana Cabrera
Affiliation:
Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain
Julio Bobes
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Psychiatry, School of Medicine, University of Oviedo, Oviedo, Spain Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain Mental Health Services of Principado de Asturias, SESPA, Oviedo, Spain
Pilar A. Saiz
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Psychiatry, School of Medicine, University of Oviedo, Oviedo, Spain Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain Mental Health Services of Principado de Asturias, SESPA, Oviedo, Spain
María Paz García-Portilla
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Psychiatry, School of Medicine, University of Oviedo, Oviedo, Spain Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain Mental Health Services of Principado de Asturias, SESPA, Oviedo, Spain
Julio Sanjuan
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Psychiatry, Hospital Clínico Universitario de Valencia, School of Medicine, Universidad de Valencia, INCLIVA, Valencia, Spain
Eduardo J. Aguilar
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Psychiatry, Hospital Clínico Universitario de Valencia, School of Medicine, Universidad de Valencia, INCLIVA, Valencia, Spain
José Luis Santos
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Psychiatry, Hospital Virgen de la Luz, Cuenca, Spain
Estela Jiménez-López
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Universidad de Castilla-La Mancha, Health and Social Research Center, Cuenca, Spain
Manuel Arrojo
Affiliation:
Department of Psychiatry, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela, SERGAS, Santiago de Compostela, Spain
Angel Carracedo
Affiliation:
Fundación Publica Galega de Medicina Xenómica, Hospital Clínico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
Gonzalo López
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Javier González-Peñas
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Mara Parellada
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Nadja P. Maric
Affiliation:
Faculty of Medicine, University of Belgrade, Belgrade, Serbia Clinic for Psychiatry CCS, Belgrade, Serbia
Cem Atbaşoğlu
Affiliation:
Department of Psychiatry, School of Medicine, Ankara University, Ankara, Turkey
Alp Ucok
Affiliation:
Department of Psychiatry, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
Köksal Alptekin
Affiliation:
Department of Psychiatry, Dokuz Eylul University School of Medicine, Izmir, Turkey
Meram Can Saka
Affiliation:
Department of Psychiatry, School of Medicine, Ankara University, Ankara, Turkey
Celso Arango
Affiliation:
Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
Michael O'Donovan
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK
Bart P. F. Rutten
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
Sinan Guloksuz
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
*
Author for correspondence: Jim van Os, E-mail: j.j.vanos-2@umcutrecht.nl
Get access Rights & Permissions[Opens in a new window]

Abstract

Background

First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.

Methods

We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.

Results

In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.

Conclusions

The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

Keywords

Cognitiongeneticsschizophreniaschizotypy
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 11 , August 2020 , pp. 1884 - 1897
Check for updates
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Genetic Risk and Outcome of Psychosis (GROUP) Investigators in EUGEI (GROUP-EUGEI) investigators are: Behrooz Z. Alizadeha, Therese van Amelsvoortb, Richard Bruggemana, Wiepke Cahnc,d, Lieuwe de Haane, Bart P. F. Ruttenb, Jurjen J. Luykxc,f, Jim van Osc,b,g and Ruud van Winkelb,h;

aUniversity of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, Groningen, The Netherlands; bMaastricht University Medical Center, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht, The Netherlands; cUniversity Medical Center Utrecht, Department of Psychiatry, UMC Utrecht Brain Centre, Utrecht University, Utrecht, The Netherlands; dAltrecht, General Menthal Health Care, Utrecht, The Netherlands; eAmsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands; fGGNet Mental Health, Apeldoorn, The Netherlands; gKing's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK and hKU Leuven, Department of Neuroscience, Research Group Psychiatry, Leuven, Belgium.

References

Addington, D, Addington, J and Maticka-Tyndale, E (1993) Assessing depression in schizophrenia: the Calgary Depression Scale. British Journal of Psychiatry Supplement 22, 39–44.CrossRefGoogle Scholar
Agerbo, E, Sullivan, PF, Vilhjalmsson, BJ, Pedersen, CB, Mors, O, Borglum, AD, Hougaard, DM, Hollegaard, MV, Meier, S, Mattheisen, M, Ripke, S, Wray, NR and Mortensen, PB (2015) Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis. JAMA Psychiatry 72, 635–641.CrossRefGoogle ScholarPubMed
Andreasen, NC (1982) Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 39, 784–788.CrossRefGoogle ScholarPubMed
Blyler, CR, Gold, JM, Iannone, VN and Buchanan, RW (2000) Short form of the WAIS-III for use with patients with schizophrenia. Schizophrenia Research 46, 209–215.CrossRefGoogle ScholarPubMed
Das, S, Forer, L, Schonherr, S, Sidore, C, Locke, AE, Kwong, A, Vrieze, SI, Chew, EY, Levy, S, McGue, M, Schlessinger, D, Stambolian, D, Loh, PR, Iacono, WG, Swaroop, A, Scott, LJ, Cucca, F, Kronenberg, F, Boehnke, M, Abecasis, GR and Fuchsberger, C (2016) Next-generation genotype imputation service and methods. Nature Genetics 48, 1284–1287.CrossRefGoogle ScholarPubMed
European Network of National Networks studying Gene–Environment Interactions in Schizophrenia, van Os, J, Rutten, BP, Myin-Germeys, I, Delespaul, P, Viechtbauer, W, van Zelst, C, Bruggeman, R, Reininghaus, U, Morgan, C, Murray, RM, Di Forti, M, McGuire, P, Valmaggia, LR, Kempton, MJ, Gayer-Anderson, C, Hubbard, K, Beards, S, Stilo, SA, Onyejiaka, A, Bourque, F, Modinos, G, Tognin, S, Calem, M, O'Donovan, MC, Owen, MJ, Holmans, P, Williams, N, Craddock, N, Richards, A, Humphreys, I, Meyer-Lindenberg, A, Leweke, FM, Tost, H, Akdeniz, C, Rohleder, C, Bumb, JM, Schwarz, E, Alptekin, K, Ucok, A, Saka, MC, Atbasoglu, EC, Guloksuz, S, Gumus-Akay, G, Cihan, B, Karadag, H, Soygur, H, Cankurtaran, ES, Ulusoy, S, Akdede, B, Binbay, T, Ayer, A, Noyan, H, Karadayi, G, Akturan, E, Ulas, H, Arango, C, Parellada, M, Bernardo, M, Sanjuan, J, Bobes, J, Arrojo, M, Santos, JL, Cuadrado, P, Rodriguez Solano, JJ, Carracedo, A, Garcia Bernardo, E, Roldan, L, Lopez, G, Cabrera, B, Cruz, S, Diaz Mesa, EM, Pouso, M, Jimenez, E, Sanchez, T, Rapado, M, Gonzalez, E, Martinez, C, Sanchez, E, Olmeda, MS, de Haan, L, Velthorst, E, van der Gaag, M, Selten, JP, van Dam, D, van der Ven, E, van der Meer, F, Messchaert, E, Kraan, T, Burger, N, Leboyer, M, Szoke, A, Schurhoff, F, Llorca, PM, Jamain, S, Tortelli, A, Frijda, F, Vilain, J, Galliot, AM, Baudin, G, Ferchiou, A, Richard, JR, Bulzacka, E, Charpeaud, T, Tronche, AM, De Hert, M, van Winkel, R, Decoster, J, Derom, C, Thiery, E, Stefanis, NC, Sachs, G, Aschauer, H, Lasser, I, Winklbaur, B, Schlogelhofer, M, Riecher-Rossler, A, Borgwardt, S, Walter, A, Harrisberger, F, Smieskova, R, Rapp, C, Ittig, S, Soguel-dit-Piquard, F, Studerus, E, Klosterkotter, J, Ruhrmann, S, Paruch, J, Julkowski, D, Hilboll, D, Sham, PC, Cherny, SS, Chen, EY, Campbell, DD, Li, M, Romeo-Casabona, CM, Emaldi Cirion, A, Urruela Mora, A, Jones, P, Kirkbride, J, Cannon, M, Rujescu, D, Tarricone, I, Berardi, D, Bonora, E, Seri, M, Marcacci, T, Chiri, L, Chierzi, F, Storbini, V, Braca, M, Minenna, MG, Donegani, I, Fioritti, A, La Barbera, D, La Cascia, CE, Mule, A, Sideli, L, Sartorio, R, Ferraro, L, Tripoli, G, Seminerio, F, Marinaro, AM, McGorry, P, Nelson, B, Amminger, GP, Pantelis, C, Menezes, PR, Del-Ben, CM, Gallo Tenan, SH, Shuhama, R, Ruggeri, M, Tosato, S, Lasalvia, A, Bonetto, C, Ira, E, Nordentoft, M, Krebs, MO, Barrantes-Vidal, N, Cristobal, P, Kwapil, TR, Brietzke, E, Bressan, RA, Gadelha, A, Maric, NP, Andric, S, Mihaljevic, M and Mirjanic, T (2014) Identifying gene–environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations. Schizophrenia Bulletin 40, 729–736.Google ScholarPubMed
Genetic Risk and Outcome in Psychosis Investigators (2011) Evidence that familial liability for psychosis is expressed as differential sensitivity to cannabis: an analysis of patient-sibling and sibling-control pairs. Archives of General Psychiatry 68, 138–147.CrossRefGoogle Scholar
Guloksuz, S and van Os, J (2018) The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum. Psychological Medicine 48, 229–244.CrossRefGoogle ScholarPubMed
Guloksuz, S, Pries, LK, Delespaul, P, Kenis, G, Luykx, JJ, Lin, BD, Richards, AL, Akdede, B, Binbay, T, Altinyazar, V, Yalincetin, B, Gumus-Akay, G, Cihan, B, Soygur, H, Ulas, H, Cankurtaran, E, Kaymak, SU, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Bernardo, M, Cabrera, B, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Sanjuan, J, Aguilar, EJ, Santos, JL, Jimenez-Lopez, E, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Maric, NP, Atbasog Lu, C, Ucok, A, Alptekin, K, Saka, MC, Genetic, R, Outcome of Psychosis i, Arango, C, O'Donovan, M, Rutten, BPF and van Os, J (2019) Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study. World Psychiatry 18, 173–182.CrossRefGoogle ScholarPubMed
Hatzimanolis, A, Bhatnagar, P, Moes, A, Wang, R, Roussos, P, Bitsios, P, Stefanis, CN, Pulver, AE, Arking, DE, Smyrnis, N, Stefanis, NC and Avramopoulos, D (2015) Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood. American Journal of Medical Genetics B – Neuropsychiatric Genetics 168B, 392–401.CrossRefGoogle ScholarPubMed
Hatzimanolis, A, Avramopoulos, D, Arking, DE, Moes, A, Bhatnagar, P, Lencz, T, Malhotra, AK, Giakoumaki, SG, Roussos, P, Smyrnis, N, Bitsios, P and Stefanis, NC (2018) Stress-dependent association between polygenic risk for schizophrenia and schizotypal traits in young army recruits. Schizophrenia Bulletin 44, 338–347.CrossRefGoogle ScholarPubMed
Heins, M, Simons, C, Lataster, T, Pfeifer, S, Versmissen, D, Lardinois, M, Marcelis, M, Delespaul, P, Krabbendam, L, van Os, J and Myin-Germeys, I (2011) Childhood trauma and psychosis: a case-control and case-sibling comparison across different levels of genetic liability, psychopathology, and type of trauma. American Journal of Psychiatry 168, 1286–1294.CrossRefGoogle ScholarPubMed
Howes, OD and Murray, RM (2014) Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 383, 1677–1687.CrossRefGoogle ScholarPubMed
Hubbard, L, Tansey, KE, Rai, D, Jones, P, Ripke, S, Chambert, KD, Moran, JL, McCarroll, SA, Linden, DE, Owen, MJ, O'Donovan, MC, Walters, JT and Zammit, S (2016) Evidence of common genetic overlap between schizophrenia and cognition. Schizophrenia Bulletin 42, 832–842.CrossRefGoogle ScholarPubMed
Jones, HJ, Stergiakouli, E, Tansey, KE, Hubbard, L, Heron, J, Cannon, M, Holmans, P, Lewis, G, Linden, DE, Jones, PB, Davey Smith, G, O'Donovan, MC, Owen, MJ, Walters, JT and Zammit, S (2016) Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population. JAMA Psychiatry 73, 221–228.CrossRefGoogle ScholarPubMed
Kapur, S, Phillips, AG and Insel, TR (2012) Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? Molecular Psychiatry 17, 1174–1179.CrossRefGoogle Scholar
Kendler, KS (2015) A joint history of the nature of genetic variation and the nature of schizophrenia. Molecular Psychiatry 20, 77–83.CrossRefGoogle ScholarPubMed
Kendler, KS, Lieberman, JA and Walsh, D (1989) The structured interview for schizotypy (SIS): a preliminary report. Schizophrenia Bulletin 15, 559–571.CrossRefGoogle ScholarPubMed
Konings, M, Bak, M, Hanssen, M, van Os, J and Krabbendam, L (2006) Validity and reliability of the CAPE: a self-report instrument for the measurement of psychotic experiences in the general population. Acta Psychiatrica Scandinavica 114, 55–61.CrossRefGoogle ScholarPubMed
Korver, N, Quee, PJ, Boos, HB, Simons, CJ and de Haan, L and GROUP Investigators (2012) Genetic Risk and Outcome of Psychosis (GROUP), a multi-site longitudinal cohort study focused on gene–environment interaction: objectives, sample characteristics, recruitment and assessment methods. International Journal of Methods in Psychiatric Research 21, 205–221.CrossRefGoogle ScholarPubMed
Lencz, T, Knowles, E, Davies, G, Guha, S, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, Mukherjee, S, DeRosse, P, Lundervold, A, Steen, VM, John, M, Espeseth, T, Raikkonen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Ikeda, M, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Horan, M, Donohoe, G, Morris, D, Corvin, A, Gill, M, Pendleton, N, Iwata, N, Darvasi, A, Bitsios, P, Rujescu, D, Lahti, J, Hellard, SL, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC and Malhotra, AK (2014) Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT). Molecular Psychiatry 19, 168–174.CrossRefGoogle Scholar
Loh, PR, Danecek, P, Palamara, PF, Fuchsberger, C, AR, Y, KF, H, Schoenherr, S, Forer, L, McCarthy, S, Abecasis, GR, Durbin, R and LP, A (2016) Reference-based phasing using the Haplotype Reference Consortium panel. Nature Genetics 48, 1443–1448.CrossRefGoogle ScholarPubMed
McGue, M, Gottesman, II and Rao, DC (1983) The transmission of schizophrenia under a multifactorial threshold model. American Journal of Human Genetics 35, 1161–1178.Google Scholar
McLean, BF, Mattiske, JK and Balzan, RP (2017) Association of the jumping to conclusions and evidence integration biases with delusions in psychosis: a detailed meta-analysis. Schizophrenia Bulletin 43, 344–354.Google ScholarPubMed
Mistry, S, Harrison, JR, Smith, DJ, Escott-Price, V and Zammit, S (2017) The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: systematic review. Schizophrenia Research. Epub ahead of print. doi:10.1016/j.schres.2017.10.037Google ScholarPubMed
Nivard, MG, Gage, SH, Hottenga, JJ, van Beijsterveldt, CEM, Abdellaoui, A, Bartels, M, Baselmans, BML, Ligthart, L, Pourcain, BS, Boomsma, DI, Munafo, MR and Middeldorp, CM (2017) Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development. Schizophrenia Bulletin 43, 1197–1207.CrossRefGoogle ScholarPubMed
Phillips, LD and Edwards, W (1966) Conservatism in a simple probability inference task. Journal of Experimental Psychology 72, 346–354.CrossRefGoogle Scholar
Power, RA, Steinberg, S, Bjornsdottir, G, Rietveld, CA, Abdellaoui, A, Nivard, MM, Johannesson, M, Galesloot, TE, Hottenga, JJ, Willemsen, G, Cesarini, D, Benjamin, DJ, Magnusson, PK, Ullen, F, Tiemeier, H, Hofman, A, van Rooij, FJ, Walters, GB, Sigurdsson, E, Thorgeirsson, TE, Ingason, A, Helgason, A, Kong, A, Kiemeney, LA, Koellinger, P, Boomsma, DI, Gudbjartsson, D, Stefansson, H and Stefansson, K (2015) Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nature Neuroscience 18, 953–955.CrossRefGoogle ScholarPubMed
Price, AL, Weale, ME, Patterson, N, Myers, SR, Need, AC, Shianna, KV, Ge, D, Rotter, JI, Torres, E, Taylor, KD, Goldstein, DB and Reich, D (2008) Long-range LD can confound genome scans in admixed populations. American Journal of Human Genetics 83, 132–135, author reply 135–9.CrossRefGoogle ScholarPubMed
Pries, LK, Klingenberg, B, Menne-Lothmann, C, Decoster, J, van Winkel, R, Collip, D, Delespaul, P, De Hert, M, Derom, C, Thiery, E, Jacobs, N, Wichers, M, Cinar, O, Lin, BD, Luykx, JJ, Rutten, BFP, van Os, J and Guloksuz, S (2019). Interaction between polygenic liability for schizophrenia and childhood adversity influences daily-life emotional dysregulation and subtle psychosis expression. Submitted Manuscript.Google Scholar
Purcell, S, Neale, B, Todd-Brown, K, Thomas, L, Ferreira, MA, Bender, D, Maller, J, Sklar, P, de Bakker, PI, Daly, MJ and Sham, PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics 81, 559–575.CrossRefGoogle ScholarPubMed
Richards, AL, Pardinas, AF, Frizzati, A, Tansey, KE, Lynham, AJ, Holmans, P, Legge, SE, Savage, JE, Agartz, I, Andreassen, OA, Blokland, GAM, Corvin, A, Cosgrove, D, Degenhardt, F, Djurovic, S, Espeseth, T, Ferraro, L, Gayer-Anderson, C, Giegling, I, van Haren, NE, Hartmann, AM, Hubert, JJ, Jonsson, EG, Konte, B, Lennertz, L, Olde Loohuis, LM, Melle, I, Morgan, C, Morris, DW, Murray, RM, Nyman, H, Ophoff, RA, Investigators, G, van Os, J, Group, EW, Schizophrenia Working Group of the Psychiatric Genomics C, Petryshen, TL, Quattrone, D, Rietschel, M, Rujescu, D, Rutten, BPF, Streit, F, Strohmaier, J, Sullivan, PF, Sundet, K, Wagner, M, Escott-Price, V, Owen, MJ, Donohoe, G, O'Donovan, MC and Walters, JTR (2019) The relationship between polygenic risk scores and cognition in schizophrenia. Schizophrenia Bulletin. Epub ahead of print. doi: 10.1093/schbul/sbz061CrossRefGoogle Scholar
Riglin, L, Collishaw, S, Richards, A, Thapar, AK, Maughan, B, O'Donovan, MC and Thapar, A (2017) Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: a population-based cohort study. The Lancet Psychiatry 4, 57–62.CrossRefGoogle ScholarPubMed
Rothman, KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1, 43–46.CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427.CrossRefGoogle Scholar
Selten, JP, Sijben, NE, van den Bosch, RJ, Omloo Visser, J and Warmerdam, H (1993) The subjective experience of negative symptoms: a self-rating scale. Comprehensive Psychiatry 34, 192–197.CrossRefGoogle ScholarPubMed
Smith, MJ, Barch, DM, Wolf, TJ, Mamah, D and Csernansky, JG (2008) Elevated rates of substance use disorders in non-psychotic siblings of individuals with schizophrenia. Schizophrenia Research 106, 294–299.CrossRefGoogle ScholarPubMed
StataCorp (2017) STATA Statistical Software: Release 15. Texas: College Station.Google Scholar
Van Dael, F, Versmissen, D, Janssen, I, Myin-Germeys, I, van Os, J and Krabbendam, L (2006) Data gathering: biased in psychosis? Schizophrenia Bulletin 32, 341–351.CrossRefGoogle ScholarPubMed
van Os, J, Kenis, G and Rutten, BP (2010) The environment and schizophrenia. Nature 468, 203–212.CrossRefGoogle Scholar
van Os, J, van der Steen, Y, Islam, MA, Guloksuz, S, Rutten, BP, Simons, CJ and Investigators, G (2017) Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience. Psychological Medicine 47, 2421–2437.CrossRefGoogle ScholarPubMed
Velthorst, E, Levine, SZ, Henquet, C, de Haan, L, van Os, J, Myin-Germeys, I and Reichenberg, A (2013) To cut a short test even shorter: reliability and validity of a brief assessment of intellectual ability in schizophrenia – a control-case family study. Cognitive Neuropsychiatry 18, 574–593.CrossRefGoogle Scholar
Vollema, MG and Ormel, J (2000) The reliability of the structured interview for schizotypy-revised. Schizophrenia Bulletin 26, 619–629.CrossRefGoogle ScholarPubMed
Wechsler, D (1997) WAIS-III: Wechsler Adult Intelligence Scale. Administration and Scoring Manual, 3rd Edn. San Antonio, TX: Psychological Corporation.Google Scholar
Wing, JK, Cooper, JE and Sartorius, N (1974) The Measurement and Classification of Psychiatric Symptoms. London: Cambridge University Press.Google Scholar