title: The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research.
abstract: Schizophrenia is a devastating mental disorder. The level of risk in the general population is sustained by the persistence of social, environmental and biological factors, as well as their interactions. Socio-environmental risk factors for schizophrenia are well established and robust. The same can belatedly be said of genetic risk factors for the disorder. Recent progress in schizophrenia genetics is primarily fuelled by genome-wide association, which is able to leverage substantial proportions of additional explained variance previously classified as 'missing'. Here, we provide an outline of the emerging genetic landscape of schizophrenia and demonstrate how this knowledge can be turned into a simple empirical measure of genetic risk, known as a polygenic risk score. We highlight the statistical framework used to assess the clinical potential of the new score and finally, draw relevance to and discuss the clinical implications for the study of gene-environment interaction.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College, London, UK, c.iyegbe@iop.kcl.ac.uk.
authors.forename: Conrad
authors.initials: C
authors.lastname: Iyegbe
authors.forename: Desmond
authors.initials: D
authors.lastname: Campbell
authors.forename: Amy
authors.initials: A
authors.lastname: Butler
authors.forename: Olesya
authors.initials: O
authors.lastname: Ajnakina
authors.forename: Pak
authors.initials: P
authors.lastname: Sham
mesh_terms: D004777:Environment; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008960:Models, Psychological; D015233:Models, Statistical; D008967:Molecular Biology / Q000379:methods*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D012931:Social Environment