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Table 1 Summary of the 28 genome-wide significant urate loci detected by Köttgen and colleagues [4]

From: An update on the genetic architecture of hyperuricemia and gout

  GRAIL gene Effect size (male/female a ), mg/dL FEUA, Yes/No b Association signal Probable causal gene c Strongest candidate(s) d,e
Old loci       
Rs1471633 PDZK1 0.059 No Within PDZK1 PDZK1 -
Rs1260326 GCKR 0.074 (0.091/0.063) Yes Spans >20 genes - GCKR
Rs12498742 SLC2A9 0.373 (0.269/0.460) Yes Spans 4 genes SLC2A9 -
Rs2231142 ABCG2 0.217 (0.280/0.181) Yes Spans 4 genes ABCG2 -
Rs675209 RREB1 0.061 Yes Upstream and within RREB1 - RREB1
Rs1165151 SLC17A3 0.091 No Spans 20 genes - SLC17A1-A4
Rs1171614 SLC16A9 0.079 No Spans 2 genes - -
Rs2078267 SLC22A11 0.073 Yes Within SLC22A11 SLC22A11 -
Rs478607 SLC22A12 0.047 Yes Spans 6 genes - SLC22A12
Rs3741414 INHBC 0.072 (0.091/0.057) No Spans 7 genes - -
New loci       
Rs11264341 PKLR 0.050 No Spans 2 genes - -
Rs17050272 INHBB 0.035 No Intergenic INHBB -
Rs2307384 ACVR2A 0.029 No Spans 3 genes - -
Rs6770152 MUSTN1 0.044 No Spans 3 genes - -
Rs17632159 TMEM171 0.039 No Intergenic - -
Rs729761 VEGFA 0.047 No Intergenic - -
Rs1178977 MLXIPL 0.047 No Spans 5 genes - MLXIPL
Rs10480300 PRKAG2 0.035 No Within PRKAG2 - PRKAG2
Rs17786744 STC1 0.029 No Intergenic - -
Rs2941484 HNF4G 0.044 No Within HNF4G   HNF4G
Rs10821905 ASAH2 0.057 No Within A1CF   A1CF
Rs642803 LTBP3 0.036 No Spans 6 genes - -
Rs653178 PTPN11 f 0.035 No Spans 3 genes - -
Rs1394125 NRG4 0.043 (0.061/0.032) Yes Spans 4 genes - -
Rs6598541 IGF1R 0.043 Yes Within IGFR1 - IGFR1
Rs7193778 NFAT5 0.046 Yes Intergenic - -
Rs7188445 MAF 0.032 No Intergenic - -
Rs7224610 HLF 0.042 Yes Within HLF - HLF
Rs2079742 C17ORF82 0.043 No Downstream and within BCAS3 - -
Rs164009 PRPSAP1 0.028 No Within QRICH2 - -
  1. aMale and female effect sizes are given for loci where there was a significant sex-specific difference. bFractional excretion of uric acid (FEUA) was tested by Köttgen and colleagues [4] on a considerably smaller subset (n = 6,799), meaning that inadequate power may contribute to lack of association seen at loci of weaker effect. cA probable causal gene either has very strong functional evidence (SLC2A9 and ABCG2) or has strong functional evidence combined with association signal restricted to the gene (PDZK1 and SLC22A11) or has very strong expression single-nucleotide polymorphism (eSNP) evidence (INHBB). dA ‘strongest candidate’ is listed when the locus contains a candidate with strong functional evidence (GCKR, SLC17A1-A4, and SLC22A12) or has the association signal tightly restricted to the named gene or has strong eSNP evidence (MLXIPL). eRREB1, ras responsive element (zinc-finger) binding protein, has been genetically implicated in type 2 diabetes associated end-stage kidney disease [60]. PRKAG2, protein kinase, AMP-activated, gamma 2 non-catalytic subunit, has been genetically implicated in blood pressure control [61]. HNF4G, hepatocyte nuclear factor 4G, has been genetically implicated in obesity [62]. MLXIPL, carbohydrate element-responsive binding protein, has been identified as a pleiotropic gene for metabolic syndrome and inflammation [63]. f PTPN11 is approximately 1 Mb downstream of the association signal and does not harbor any association signal. A1CF, APOBEC1 (APOB mRNA editing enzyme) complementation factor; GRAIL, Gene Relationships Across Implicated Loci; HLF, hepatic leukemia factor; IGFR1, insulin-like growth factor 1 receptor.