ArticlePsychological medicine2025
Uncovering the genetic underpinnings for different psychiatric disorder combinations.
Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPsychiatric disorders are highly heterogeneous. It is clinically valuable to distinguish psychiatric disorders by the presence or absence of a specific comorbid condition.
methodsWe employed a novel algorithm (CombGWAS) to decipher the genetic basis of psychiatric disorder combinations using genome-wide association studies summary statistics. We focused on comorbidities and combinations of diseases, such as schizophrenia (SCZ) with and without depression, which can be considered as two 'subtypes' of SCZ. We also studied psychiatric disorders comorbid with obesity as disease subtypes.
resultsWe compared the genetic architectures of psychiatric disorders with and without specific comorbidities, identifying both shared and unique susceptibility genes/variants across 8 subtype pairs (16 entities). Despite high genetic correlations between subtypes, most subtype pairs exhibited distinct genetic correlations with the same cardiovascular disease (CVD). Some pairs even displayed opposite genetic correlations, especially those involving obesity. For instance, the genetic correlation (rg) between SCZ with obesity and type 2 diabetes (T2DM) was 0.248 (
conclusionsOur study provides novel insights into the genetic basis of psychiatric disorder heterogeneity, revealing unique genetic signatures across various disorder combinations. Notably, comorbid psychiatric disorders often showed different causal relationships with CVD compared to single disorders.
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