论文标题
分析精神疾病之间的遗传差异：探索所涉及的途径和细胞类型/组织以及通过多基因分数区分疾病的能力
Analysis of genetic differences between psychiatric disorders: Exploring pathways and cell-types/tissues involved and ability to differentiate the disorders by polygenic scores
论文作者
论文摘要
尽管表现出遗传相关性，但精神疾病在临床上被定义为分类实体，因为它们各自具有临床特征，并且可能涉及不同的治疗方法。识别这些疾病之间的差异遗传变异可能会揭示疾病在生物学上有何不同并有助于指导更多个性化的治疗方法。 在这里，我们提出了一项全面的分析，以确定基于GWAS摘要统计数据与各种精神疾病/特征差异相关的遗传标记，涵盖了18种精神病性状/疾病和26个比较。我们还进行了全面的分析，以揭示所涉及的基因，途径和SNP功能类别以及所涉及的细胞类型和组织。我们还评估了人们如何通过多基因风险评分（PRS）区分精神疾病。 对于大多数比较，基于SNP的遗产（H2SNP）明显大于零。根据当前的GWAS数据，PRS主要具有区分精神疾病的大部分功能。例如，我们估计，将精神分裂症与主要抑郁症（MDD），MDD的双相情感障碍（BPD）和BPD的AUC分别为0.694、0.602和0.618，而最大AUC（基于H2SNP）为0.763、0.763、0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.749和0.726。我们还发现，每对研究性状的差异在与合并性状的遗传相关性上的差异方面存在。例如，与英国生物库中的非临床定义的抑郁症相比，临床定义的MDD似乎与其他精神疾病和心脏病的遗传相关。 我们的发现突出了精神疾病与所涉及的机制之间的遗传差异。 PRS可能会在未来使用较大的GWAS样本来帮助对选定的精神疾病进行鉴别诊断。
Although displaying genetic correlations, psychiatric disorders are clinically defined as categorical entities as they each have distinguishing clinical features and may involve different treatments. Identifying differential genetic variations between these disorders may reveal how the disorders differ biologically and help to guide more personalized treatment. Here we presented a comprehensive analysis to identify genetic markers differentially associated with various psychiatric disorders/traits based on GWAS summary statistics, covering 18 psychiatric traits/disorders and 26 comparisons. We also conducted comprehensive analysis to unravel the genes, pathways and SNP functional categories involved, and the cell types and tissues implicated. We also assessed how well one could distinguish between psychiatric disorders by polygenic risk scores (PRS). SNP-based heritabilities (h2SNP) were significantly larger than zero for most comparisons. Based on current GWAS data, PRS have mostly modest power to distinguish between psychiatric disorders. For example, we estimated that AUC for distinguishing schizophrenia from major depressive disorder (MDD), bipolar disorder (BPD) from MDD and schizophrenia from BPD were 0.694, 0.602 and 0.618 respectively, while the maximum AUC (based on h2SNP) were 0.763, 0.749 and 0.726 respectively. We also uncovered differences in each pair of studied traits in terms of their differences in genetic correlation with comorbid traits. For example, clinically-defined MDD appeared to more strongly genetically correlated with other psychiatric disorders and heart disease, when compared to non-clinically-defined depression in UK Biobank. Our findings highlight genetic differences between psychiatric disorders and the mechanisms involved. PRS may aid differential diagnosis of selected psychiatric disorders in the future with larger GWAS samples.
