Fig. 5: Effects of CAG architecture and allelic variants. | Nature Medicine

Fig. 5: Effects of CAG architecture and allelic variants.

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

Fig. 5

a, Illustration of the HTT repeat structure and allelic variations in the HDGE cohort (n = 72), including the typical structure and four atypical variants—CAACAG duplication (green), CAACAG loss (black, not observed in cohort), CAACAG CCGCCA loss (red) and CCGCCA loss (blue). b, Illustration of atypical allele differences for key biomarker measures. The ANOCOVA models controlled for CAG length, sex and age, including age interactions with CAG and sex. Participant-specific random effects were included except for caudate change based on one boundary-shift integral per participant. (i) The effect on caudate volume change, with significant differences between typical alleles and CAACAG CCGCCA loss (P < 0.0001) and a trend with CCGCCA loss (P = 0.050). (ii) The effect on putamen volume change, with significant differences between typical alleles and CAACAG CCGCCA loss (P = 0.007). (iii and iv) Cross-sectional effects on CSF NfL (iii) and CSF PENK (iv) levels, respectively, with significant differences noted for CAACAG CCGCCA loss. Statistically significant comparisons (P < 0.05) are indicated by asterisks. Please note no longitudinal imaging for CAACAG duplication, hence no plot in (i) or (ii).

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