Figure 3.

Overlap between natural selection signatures and genetic risk of gout and its subtypes in the Japanese population. For each trait, inflation of the selection χ² value is indicated along the x-axis, and −log₁₀(p) of enrichment is plotted along the y-axis. The horizontal grey line represents significance threshold (p<0.05). Because ABCG2 and ALDH2 are associated with a well-known genetic risk of gout in Japanese individuals, selection pressure analyses without these loci were performed initially (filled circle), and subsequent analyses were conducted with ABCG2 (filled triangle), as well as ABCG2 and ALDH2 (filled square). When calculated with ABCG2 (outside of ALDH2) (filled triangle), all but normal type gout showed significant selective pressure, indicating that ABCG2 is involved in adaptive evolution in Japanese for having higher SUA levels, which can result in gout. Finally, all but normal type gout also showed significant selective pressure with ABCG2 and ALDH2 loci (filled square). ROL, renal overload; RUE, renal underexcretion; SDS, singleton density score; SNPs, single-nucleotide polymorphisms.