The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition of monosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with the strongest effects, mapping mainly to genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants. More recently, genetic and epigenetic genome-wide studies have revealed new pathways in the inflammatory process of gout, including genetic associations with epigenomic modifiers. Epigenome-wide association studies are also implicating epigenomic remodelling in gout, which perhaps regulates the responsiveness of the innate immune system to monosodium urate crystals. Notably, genes implicated in gout GWAS do not include those encoding components of the NLRP3 inflammasome itself, but instead include genes encoding molecules involved in its regulation. Knowledge of the molecular mechanisms underlying gout has advanced through the translation of genetic associations into specific molecular mechanisms. Notable examples include ABCG2, HNF4A, PDZK1, MAF and IL37. Current genetic studies are dominated by participants of European ancestry; however, studies focusing on other population groups are discovering informative population-specific variants associated with gout.

痛风的发病机制涉及一系列步骤，从高尿酸血症开始，随后尿酸钠晶体沉积在关节结构中，最终导致由 NLRP3 炎性体介导的对沉积晶体的先天免疫反应。血清尿酸水平的大型全基因组关联研究（GWAS）最初确定了影响最强的遗传变异，主要映射到编码肾脏和肠道尿酸转运蛋白的基因。其他 GWAS 强调了不常见遗传变异的重要性。最近，遗传和表观遗传全基因组研究揭示了痛风炎症过程的新途径，包括与表观基因组修饰因子的遗传关联。全表观基因组关联研究也表明痛风中的表观基因组重塑可能调节先天免疫系统对单钠尿酸盐晶体的反应。值得注意的是，与痛风 GWAS 相关的基因不包括那些编码 NLRP3 炎症小体本身成分的基因，而是包括编码参与其调节的分子的基因。通过将遗传关联转化为特定的分子机制，对痛风分子机制的了解不断深入。值得注意的例子包括ABCG2 、 HNF4A 、 PDZK1 、 MAF和IL37 。目前的遗传学研究主要由欧洲血统的参与者主导。然而，针对其他人群的研究正在发现与痛风相关的特定人群变异。