Dissecting the relationship between cognition and psychiatric disorders using genetics

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The relationship between cognition and psychiatric disorder is disorder-dependent, with biological and psychosocial components. In schizophrenia, cognitive impairment is a core feature, with cognitive deficits often predating the onset of psychosis. In depression, cognitive impairment is observed during major depressive episodes, and may continue beyond recovery from the mood disorder symptoms, impacting quality of life and functioning. Disentangling the clinical, social and genetic features of cognition in psychiatry is challenging, but genetic studies permit us to discriminate the independent and joint contributions to cognition and psychiatric disorders. This PhD project will use genetic tools to determine the relationship between cognition and the two psychiatric disorders of depression (at King's College London) and schizophrenia (at Genome Institute of Singapore; A*STAR) to gain insights into the core biological contributions, and how they act. Year 1 (King's): Assess the three-way relationship between depression, educational attainment and cognition, phenotypically and genetically in UK Biobank. Year 2 (A*STAR, Genome Institute of Singapore): Assess the relationship between schizophrenia, education attainment and cognition using cross-ancestry methodologies recently developed. Year 3 (A*STAR, Genome Institute of Singapore): Build pleiotropic polygenic risk prediction models to estimate the probability of treatment-resistant schizophrenia Year 4 (King's): Use new cognitive data being collected shortly in UK Biobank, to assess how change in cognition (across 10-15 years) is associated with depression diagnosis, and the genetic contribution to both depression and intelligence. Expand genetic analysis to whole genome sequencing.