Fig. 1: Rare single-variant analyses.
From: Large-scale exome analyses reveal new rare variant contributions in amyotrophic lateral sclerosis
a, y axis: exome-wide single variant associations estimated using Firth’s logistic regression with profile penalized likelihood CIs (−log10(P)); x axis: genomic coordinates (GRCh38). Dashed line: exome-wide significance threshold (P < 1.83 × 10−7). New variants are highlighted in orange. b, Rare single-variant analyses among ALS-linked genes curated by the ALS GCEP. y axis: single-variant associations estimated using Firth’s logistic regression with profile penalized likelihood CIs (−log10(P)); x axis: genomic coordinates (GRCh38). Variants are colored by the clinical validity classification as curated by the ALS GCEP. Lower dashed line: significance threshold across variants in ALS-linked genes (P < 3.20 × 10−5); upper dashed line: exome-wide significance threshold as presented in a. c, ORs (y axis) and 95% CIs (gray shaded area) plotted against the risk allele frequency in controls (x axis) for significant variants identified in either the exome-wide or GCEP analysis. For variants where the control risk allele frequency was 0, it was set to half the lowest nonzero risk allele frequency observed in the control group. P values are two-tailed and are presented uncorrected for multiple testing.
