Fig. 4: Distribution of effects of rare variants in select genes in the UKB cohort. | Nature Communications

Fig. 4: Distribution of effects of rare variants in select genes in the UKB cohort.

From: Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

Fig. 4

a SLC2A9 protein and urate levels. The legend shows the gene, its associated phenotype, and the effect size (beta). The effect size is computed from the gene-based collapsing model, in which individuals were coded as either having or not having a qualifying variant. A positive value indicates that variant carriers have, on average, higher values for the phenotype, while a negative value indicates that variant carriers have lower values. The amino acid positions are shown on the x-axis, with the PFAM domain highlighted. The y-axis displays the beta of each individual variant, with negative values shown below and positive values above the horizontal axis. Variants are indicated according to their consequence as shown and labelled according to their amino acid change or splice site variation. The number inside the circle is the number of people carrying that variant. Darker lines connecting the variants to the gene and darker-filled shapes indicate more significant p values for the association. b Membrane topology plot of SLC2A9 showing variants with positive effect size (green) on urate levels and variants with negative effect size (pink). SLC2A9 (Glut9) reabsorbs urate in the proximal tubules of the kidneys. Variants that disrupt the transmembrane regions or lower gene expression are known to be associated with hypouricemia29. Here, 88% of the variants with negative betas, associated with lowered urate levels, are in or directly adjacent to a predicted transmembrane region, as opposed to only 55% of the variants with positive effect size. c GFI1B protein and mean platelet volume. Consistent with the literature, variants in the zinc finger domains are associated with increased platelet volumes, but we make the observation that some variants in between zinc fingers 3 and 4 may be having an effect in the opposite direction30,31. d ASGR1 protein and alkaline phosphatase levels. In addition to the known effects of LoF variants, we show that missense variants are also playing a role32. Plots of the other significantly associated genes are included in Supplementary Fig. 3.

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