Phenotypic annotation of common SCZ risk variant combinations
Principal Investigator: Dr Michael Ziller
Approved Research ID: 34217
Approval date: September 3rd 2018
The primary aim of this study is to identify structural, psychological/psychometric, and physiological alterations associated with combinations of genetic risk variants for schizophrenia (SCZ). The secondary aim of this study is to pinpoint environmental factors that modulate the effects of these genetic variants. We propose to leverage the genetic and phenotypic data available in the UK biobank to characterize phenotypic, potentially predisposing, consequences of subsets of SCZ associated genetic variants independent of SCZ status. This analysis will provide insights into the underlying mechanisms and components of pathophysiology underlying SCZ emergence and progression. SCZ is one of the most severe psychiatric diseases and represents one of the top 25 causes of global Years Lived with Disability. Our work is focused on understanding the distinct contributing causes and pathophysiological changes leading to onset of SCZ as well as those factors that may potentially protect from SCZ in carriers of known risk variants. Our study will pave the way for the identification of targetable molecular subsystems for pharmacological intervention, in particular in the context of drug repurposing, aiming at ?improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses?. The project will take advantage of recently identified genetic risk variants for SCZ and will use quantitative genetic analysis to explore the association of combinations of genetic risk variants and environmental factors in SCZ with 1. structural and functional brain measurements (e.g. imaging data) 2. indicators of mental health, 3. immune system status, 4. cognitive performance (e.g. psychometry). We will attempt to replicate findings in data from inhouse data and data from the psychiatric genome consortium to assess the relevance of UK biobank based findings for SCZ individuals. We want to include all participants with data on mental health and cognitive performance, as well as the sub-cohort for which imaging data is available.