scispace - formally typeset
Search or ask a question
Author

Evangelos Vassos

Bio: Evangelos Vassos is an academic researcher from King's College London. The author has contributed to research in topics: Schizophrenia & Population. The author has an hindex of 35, co-authored 117 publications receiving 7948 citations. Previous affiliations of Evangelos Vassos include National and Kapodistrian University of Athens & South London and Maudsley NHS Foundation Trust.


Papers
More filters
Journal ArticleDOI
Hreinn Stefansson1, Dan Rujescu2, Sven Cichon3, Olli Pietiläinen, Andres Ingason1, Stacy Steinberg1, Ragnheidur Fossdal1, Engilbert Sigurdsson, Thordur Sigmundsson, Jacobine E. Buizer-Voskamp4, Thomas Hansen5, Thomas Hansen6, Klaus D. Jakobsen6, Klaus D. Jakobsen5, Pierandrea Muglia7, Clyde Francks7, Paul M. Matthews8, Arnaldur Gylfason1, Bjarni V. Halldorsson1, Daniel F. Gudbjartsson1, Thorgeir E. Thorgeirsson1, Asgeir Sigurdsson1, Adalbjorg Jonasdottir1, Aslaug Jonasdottir1, Asgeir Björnsson1, Sigurborg Mattiasdottir1, Thorarinn Blondal1, Magnús Haraldsson, Brynja B. Magnusdottir, Ina Giegling2, Hans-Jürgen Möller2, Annette M. Hartmann2, Kevin V. Shianna9, Dongliang Ge9, Anna C. Need9, Caroline Crombie10, Gillian Fraser10, Nicholas Walker, Jouko Lönnqvist, Jaana Suvisaari, Annamarie Tuulio-Henriksson, Tiina Paunio, T. Toulopoulou11, Elvira Bramon11, Marta Di Forti11, Robin M. Murray11, Mirella Ruggeri12, Evangelos Vassos11, Sarah Tosato12, Muriel Walshe11, Tao Li13, Tao Li11, Catalina Vasilescu3, Thomas W. Mühleisen3, August G. Wang6, Henrik Ullum6, Srdjan Djurovic14, Ingrid Melle, Jes Olesen15, Lambertus A. Kiemeney16, Barbara Franke16, Chiara Sabatti17, Nelson B. Freimer17, Jeffrey R. Gulcher1, Unnur Thorsteinsdottir1, Augustine Kong1, Ole A. Andreassen14, Roel A. Ophoff17, Roel A. Ophoff4, Alexander Georgi18, Marcella Rietschel18, Thomas Werge6, Hannes Petursson, David Goldstein9, Markus M. Nöthen3, Leena Peltonen19, Leena Peltonen20, David A. Collier11, David A. Collier13, David St Clair10, Kari Stefansson1, Kari Stefansson21 
11 Sep 2008-Nature
TL;DR: In a genome-wide search for CNVs associating with schizophrenia, a population-based sample was used to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring and three deletions significantly associate with schizophrenia and related psychoses in the combined sample.
Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

1,767 citations

Journal ArticleDOI
Hreinn Stefansson1, Hreinn Stefansson2, Roel A. Ophoff1, Roel A. Ophoff3, Roel A. Ophoff4, Stacy Steinberg1, Stacy Steinberg2, Ole A. Andreassen5, Sven Cichon6, Dan Rujescu7, Thomas Werge8, Olli Pietilainen9, Ole Mors10, Preben Bo Mortensen11, Engilbert Sigurdsson12, Omar Gustafsson2, Mette Nyegaard11, Annamari Tuulio-Henriksson13, Andres Ingason2, Thomas Hansen8, Jaana Suvisaari13, Jouko Lönnqvist13, Tiina Paunio, Anders D. Børglum10, Anders D. Børglum11, Annette M. Hartmann7, Anders Fink-Jensen8, Merete Nordentoft14, David M. Hougaard, Bent Nørgaard-Pedersen, Yvonne Böttcher2, Jes Olesen15, René Breuer16, Hans-Jürgen Möller7, Ina Giegling7, Henrik B. Rasmussen8, Sally Timm8, Manuel Mattheisen6, István Bitter17, János Réthelyi17, Brynja B. Magnusdottir12, Thordur Sigmundsson12, Pall I. Olason2, Gisli Masson2, Jeffrey R. Gulcher2, Magnús Haraldsson12, Ragnheidur Fossdal2, Thorgeir E. Thorgeirsson2, Unnur Thorsteinsdottir12, Unnur Thorsteinsdottir2, Mirella Ruggeri18, Sarah Tosato18, Barbara Franke19, Eric Strengman3, Lambertus A. Kiemeney19, Ingrid Melle5, Srdjan Djurovic5, Lilia I. Abramova20, Kaleda Vg20, Julio Sanjuán21, Rosa de Frutos21, Elvira Bramon22, Evangelos Vassos22, Gillian Fraser23, Ulrich Ettinger22, Marco Picchioni22, Nicholas Walker, T. Toulopoulou22, Anna C. Need24, Dongliang Ge24, Joeng Lim Yoon4, Kevin V. Shianna24, Nelson B. Freimer4, Rita M. Cantor4, Robin M. Murray22, Augustine Kong2, Vera Golimbet20, Angel Carracedo25, Celso Arango26, Javier Costas, Erik G. Jönsson27, Lars Terenius27, Ingrid Agartz27, Hannes Petursson12, Markus M. Nöthen6, Marcella Rietschel16, Paul M. Matthews28, Pierandrea Muglia29, Leena Peltonen9, David St Clair23, David Goldstein24, Kari Stefansson12, Kari Stefansson2, David A. Collier22, David A. Collier30 
06 Aug 2009-Nature
TL;DR: Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.

1,625 citations

Journal ArticleDOI
TL;DR: Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis, and sufficient evidence to justify harm reduction prevention programs.
Abstract: Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs.

586 citations

Journal ArticleDOI
TL;DR: In this article , a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals was conducted, and the authors reported common variant associations at 287 distinct genomic loci.
Abstract: Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies. A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

558 citations

Journal ArticleDOI
TL;DR: How polygenic risk score may be informative at different points in the disease trajectory is considered giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.
Abstract: Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual’s susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual’s lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual’s PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.

542 citations


Cited by
More filters
Journal ArticleDOI
08 Oct 2009-Nature
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

7,797 citations

Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale2, Benjamin M. Neale1  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations

Journal ArticleDOI
Shaun Purcell1, Shaun Purcell2, Naomi R. Wray3, Jennifer Stone2, Jennifer Stone1, Peter M. Visscher, Michael Conlon O'Donovan4, Patrick F. Sullivan5, Pamela Sklar2, Pamela Sklar1, Douglas M. Ruderfer, Andrew McQuillin, Derek W. Morris6, Colm O'Dushlaine6, Aiden Corvin6, Peter Holmans4, Stuart MacGregor3, Hugh Gurling, Douglas Blackwood7, Nicholas John Craddock5, Michael Gill6, Christina M. Hultman8, Christina M. Hultman9, George Kirov4, Paul Lichtenstein9, Walter J. Muir7, Michael John Owen4, Carlos N. Pato10, Edward M. Scolnick2, Edward M. Scolnick1, David St Clair, Nigel Williams4, Lyudmila Georgieva4, Ivan Nikolov4, Nadine Norton4, Hywel Williams4, Draga Toncheva, Vihra Milanova, Emma Flordal Thelander9, Patrick Sullivan11, Elaine Kenny6, Emma M. Quinn6, Khalid Choudhury12, Susmita Datta12, Jonathan Pimm12, Srinivasa Thirumalai13, Vinay Puri12, Robert Krasucki12, Jacob Lawrence12, Digby Quested14, Nicholas Bass12, Caroline Crombie15, Gillian Fraser15, Soh Leh Kuan, Nicholas Walker, Kevin A. McGhee7, Ben S. Pickard16, P. Malloy7, Alan W Maclean7, Margaret Van Beck7, Michele T. Pato10, Helena Medeiros10, Frank A. Middleton17, Célia Barreto Carvalho10, Christopher P. Morley17, Ayman H. Fanous, David V. Conti10, James A. Knowles10, Carlos Ferreira, António Macedo18, M. Helena Azevedo18, Andrew Kirby2, Andrew Kirby1, Manuel A. R. Ferreira1, Manuel A. R. Ferreira2, Mark J. Daly1, Mark J. Daly2, Kimberly Chambert2, Finny G Kuruvilla2, Stacey Gabriel2, Kristin G. Ardlie2, Jennifer L. Moran2 
06 Aug 2009-Nature
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Abstract: Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

4,573 citations