Figure 1.

Risk allele and multilocus inheritance in inherited axonopathies. (A-C) CMT gene-based rare variant association analysis. (A) qq plot of the observed p-values from C-alpha gene-based association analysis. Blue line indicates multiple testing correction threshold. Known CMT genes with nominal significance are annotated; (B) Transcript model of EXOC4 annotated with variant positions and counts (green bubble); and (C) Heterozygous carrier risk for CMT at gene and variant level. (D-E) Cumulative mutational burden across disease genes. Distribution of the average count of qualifying variants in known HSP and CMT disease genes per case at 1% and 0.1% ExAC MAF for (D) non-synonymous and (E) loss-of-function variation. Difference in case/control distribution tested with Mann-Whitney U Test (*p-value <= 0.05). (F-I) Multilocus variant counts across disease genes. Proportion (F-G) and absolute counts (H-I) of cases carrying non-synonymous (F,H) and loss-of-function (G,I) variants in the indicated number of mutated disease genes (1, 2, 2+, or 3+) at 0.1% and 1% ExAC MAF.