Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout. This research was conducted using the UK Biobank resource. The association of alcohol consumption with serum urate and gout was tested among 458,405 European participants. Candidate SNPs were identified by comparing serum urate, gout, and alcohol consumption GWAS for shared signals of association. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of interaction terms to identify SNP-alcohol consumption interactions for association with serum urate level, hyperuricaemia, and gout. The nature of these interactions was characterised using genotype-stratified association analyses. Alcohol consumption was associated with elevated serum urate and gout. For serum urate level, non-additive interactions were identified between alcohol consumption and rs1229984 at the ADH1B locus (P = 3.0 × 10−44) and rs6460047 at the MLXIPL locus (P = 1.4 × 10−4). ADH1B also demonstrated interaction with alcohol consumption for hyperuricaemia (P = 7.9 × 10−13) and gout (P = 8.2 × 10−9). Beer intake had the most significant interaction with ADH1B for association with serum urate and gout among men, while wine intake had the most significant interaction among women. In the genotype-stratified association analyses, ADH1B and MLXIPL were associated with serum urate level and ADH1B was associated with hyperuricaemia and gout among consumers of alcohol but not non-consumers. In this large study of European participants, novel interactions with alcohol consumption were identified at ADH1B and MLXIPL for association with serum urate level and at ADH1B for association with hyperuricaemia and gout. The association of ADH1B with serum urate and gout may occur through the modulation of alcohol metabolism rate among consumers of alcohol.

中文翻译：

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ADH1B 和 MLXIPL 遗传变异与饮酒导致欧洲人血清尿酸水平升高和痛风的相互作用

饮酒是高尿酸血症和痛风的危险因素。在单独的全基因组关联研究 (GWAS) 中，多个单核苷酸多态性 (SNP) 已被确定与饮酒和血清尿酸或痛风相关。本研究旨在识别和表征这些共同的遗传关联信号与饮酒对血清尿酸水平、高尿酸血症和痛风之间的相互作用。这项研究是利用英国生物银行资源进行的。在 458,405 名欧洲参与者中测试了饮酒与血清尿酸和痛风的关联。通过比较血清尿酸盐、痛风和饮酒 GWAS 的共享关联信号来识别候选 SNP。进行多变量调整线性和逻辑回归分析，包括交互作用项，以确定 SNP-酒精消耗交互作用与血清尿酸水平、高尿酸血症和痛风的关系。使用基因型分层关联分析来表征这些相互作用的性质。饮酒与血清尿酸升高和痛风有关。对于血清尿酸盐水平，饮酒与 ADH1B 基因座的 rs1229984 (P = 3.0 × 10−44) 和 MLXIPL 基因座的 rs6460047 (P = 1.4 × 10−4) 之间存在非加性相互作用。 ADH1B 还证明了与饮酒对高尿酸血症 (P = 7.9 × 10−13) 和痛风 (P = 8.2 × 10−9) 的相互作用。在男性中，啤酒摄入量与 ADH1B 与血清尿酸和痛风的相关性最显着，而在女性中，葡萄酒摄入量与 ADH1B 的交互作用最显着。在基因型分层关联分析中，ADH1B 和 MLXIPL 与饮酒者的血清尿酸水平相关，ADH1B 与高尿酸血症和痛风相关，但与非饮酒者无关。在这项针对欧洲参与者的大型研究中，发现 ADH1B 和 MLXIPL 与血清尿酸水平相关，以及 ADH1B 与高尿酸血症和痛风相关。 ADH1B 与血清尿酸和痛风的关联可能是通过调节饮酒者的酒精代谢率而发生的。