Analysis of Genetic Differences Between Psychiatric Disorders: Exploring Pathways and Cell Types/tissues Involved and Ability to Differentiate the Disorders by Polygenic Scores

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2021 Aug 14

PMID 34389699

Authors

Shitao Rao

Liangying Yin

Yong Xiang

Hon-Cheong So

Affiliations

Soon will be listed here.

Abstract

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 statistical framework and 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 (h) 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 h) 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 help differential diagnosis of selected psychiatric disorders in the future with larger GWAS samples.

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