Extended Data Fig. 4: Conceptual causal model. | Nature Medicine

Extended Data Fig. 4: Conceptual causal model.

From: Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington’s disease decades before clinical motor diagnosis

Extended Data Fig. 4

Conceptual model illustrating the causal relationships among age-related CAG repeat length (age, CAG), CNS somatic expansion, WBC somatic expansion and biomarkers. The squares in gray depict measured data, while the circles in purple represent unobservable quantities. The black, bidirectional arrow signifies the assumption that somatic expansion in WBCs serves as a proxy for somatic expansion in the CNS. Red arrows indicate correlations between observable data and the underlying biological processes of interest. Blue arrows are presumed to reflect true causal pathways indirectly. We note that DNA mismatch repair is a key mechanism linking inherited CAG repeat length to somatic expansion, with mismatch repair activity increasing with longer CAG repeat lengths. *Note additional pathways could be involved due to the imprecise and indirect measurement of actual CNS expansion. Abbreviations: CNS=Central Nervous System. WBC=White Blood Cell.

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