Dosage-sensitive molecular mechanisms are associated with the tissue-specificity of traits and diseases.

摘要: Hereditary diseases and complex traits often manifest in specific tissues, whereas their causal genes are expressed many tissues that remain unaffected. Among the mechanisms have been suggested for this enigmatic phenomenon is dosage-sensitive compensation by paralogs of genes. Accordingly, tissue-selectivity stems from dosage imbalance between occurs particularly disease-susceptible tissues. Here, we used a large-scale dataset thousands tissue transcriptomes applied linear mixed model (LMM) framework to assess other mechanisms. LMM analysis 382 hereditary consistently showed evidence across subsets susceptible 135 candidate strongly associated with 16 tissue-selective revealed similar tendency among half trait-associated This suggests affects traits, can be illuminate genes' modes action. Next, analyze three classes genetic modifiers, including regulatory micro-RNAs, pseudogenes, interactors. Our results propose modifiers as fundamental axis demonstrates power statistical discovering treatment avenues.