To further identify genetic variants associated with serum urate concentrations and gout, several additional analyses were carried out. These included X-chromosome analyses, sex-stratified analyses, a gene-based test and urate transporter candidate analyses, as well as secondary analyses to improve the characterization of associated SNPs. To this end, we investigated associations with FEUA, associations in individuals of non-European ancestry, associations with transcript expression, associations with serum metabolite concentrations, risk score analyses and associations with other urate-related phenotypes. Secondary analyses are described in detail in the Supplementary Note.
As a result of the secondary analyses, seven additional SNPs were identified for further replication testing: one from the analysis in men only, five from the analysis in women and one from the urate transporter candidate analysis.
A new part of the secondary analyses was the implementation of functional association networks as described in the Supplementary Note. As detailed there, the approach based on functional associations among the urate genes, mostly protein-protein interactions, led to the identification of 17 additional independent SNPs in newly identified genomic regions that were subjected to replication testing. Altogether, we therefore tested 61 SNPs (37 overall, 6 sex specific, 1 urate transporter candidate and 17 network) for replication in additional study samples.