Dissecting the relationship between cognition and psychiatric disorders using genetics

认知与精神疾病之间的关系是疾病依赖性的，具有生物学和心理社会学成分。在精神分裂症中，认知障碍是一个核心特征，认知缺陷往往早于精神病发作。在抑郁症中，在重度抑郁发作期间观察到认知障碍，并且可能持续超过从情绪障碍症状中恢复，影响生活质量和功能。解开精神病学中认知的临床，社会和遗传特征是具有挑战性的，但遗传研究使我们能够区分认知和精神疾病的独立和联合贡献。这个博士项目将使用遗传工具来确定认知与抑郁症（伦敦国王学院）和精神分裂症（新加坡基因组研究所; A* 星星）这两种精神疾病之间的关系，以深入了解核心生物学贡献，以及它们如何发挥作用。第一年（国王）：评估英国生物库中抑郁症、教育程度和认知之间的表型和遗传三向关系。 第二年（A* 星星，新加坡基因组研究所）：使用最近开发的跨祖先方法评估精神分裂症，教育程度和认知之间的关系。 第3年（A* 星星，新加坡基因组研究所）：建立多效多基因风险预测模型，以估计难治性精神分裂症的概率第4年（国王）：使用英国生物银行不久收集的新认知数据，评估认知变化（10-15年）如何与抑郁症诊断相关，以及遗传对抑郁症和智力的贡献。将遗传分析扩展到全基因组测序。

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.