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Background  Sex-specific differences in the effect of genetic variants on serum urate levels have been described. The aim of this study was to systematically examine whether serum urate-associated genetic variants differ in their influence on gout risk in men and women.    Methods  This research was conducted using the UK Biobank Resource. Thirty single nucleotide polymorphisms (SNPs) associated with serum urate were tested for their association with gout in men and women of European ancestry, aged 40–69 years. Gene-sex interactions for gout risk were analysed using an interaction analysis in logistic regression models.    Results  Gout was present in 6768 (4.1%) men and 574 (0.3%) women, with an odds ratio (95% confidence interval) for men 13.42 (12.32–14.62) compared with women. In men, experiment-wide association with gout was observed for 21 of the 30 serum urate-associated SNPs tested, and in women for three of the 30 SNPs. Evidence for gene-sex interaction was observed for  ABCG2  (rs2231142) and  PDZK1  (rs1471633), with the interaction in  ABCG2  driven by an amplified effect in men and in  PDZK1  by an absence of effect in women. Similar findings were observed in a sensitivity analysis which excluded pre-menopausal women. For the other SNPs tested, no significant gene-sex interactions were observed.    Conclusions  In a large population of European ancestry,  ABCG2  and  PDZK1  gene-sex interactions exist for gout risk, with the serum urate-raising alleles exerting a greater influence on gout risk in men than in women. In contrast, other serum urate-associated genetic variants do not demonstrate significant gene-sex interactions for gout risk.    Electronic supplementary material  The online version of this article (10.1186/s13075-018-1787-5) contains supplementary material, which is available to authorized users.

Interactions between serum urate-associated genetic variants and sex on gout risk: analysis of the UK Biobank