Journal
NATURE GENETICS
Volume 45, Issue 2, Pages 145-154Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2500
Keywords
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Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: Medline
- Cancer Research UK [12076, 14136] Funding Source: Medline
- Intramural NIH HHS [Z01 AG000954-06] Funding Source: Medline
- Medical Research Council [G0401527, G0600237, G1002084, MR/K026992/1, MC_U106179471, MC_U127592696, MC_U106188470, MC_PC_U127592696, MC_PC_U127561128, MC_PC_13041, MC_UU_12015/1, MR/K006584/1, MC_U127527198, G0700704, MR/K018647/1, G9521010, G1000143] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000124] Funding Source: Medline
- NCI NIH HHS [R01 CA047988, P01 CA087969] Funding Source: Medline
- NCRR NIH HHS [UL1 RR025005, K12 RR023250, M01 RR016500] Funding Source: Medline
- NHGRI NIH HHS [U01 HG004446, U01 HG004729, U01 HG004424, U01 HG004402] Funding Source: Medline
- NHLBI NIH HHS [HHSN268201100008C, R01 HL080295, R01 HL088119, U01 HL069757, N01 HC095170, HHSN268201100012C, N01HC45204, N01HC55222, N02HL64278, N01 HC095171, N01HC85086, R01 HL105756, U01 HL084756, HHSN268201100006C, HHSN268201200036C, N01HC95095, R01 HL087641, N01HC85079, N01HC48048, HHSN268201100005C, R01 HL087652, N01 HC095172, R01 HL086694, HHSN268201100011C, R01 HL084099, N01HC48047, U01 HL072515, N01HC48049, N01HC45205, R01 HL043851, R01 HL059367, HHSN268201100007C, N01HC48050, HHSN268201100010C, N01 HC025195, N01HC75150, N01HC05187, HHSN268201100009C, N01 HC045134] Funding Source: Medline
- NIAAA NIH HHS [R01 AA013320, R01 AA013321, R01 AA014041, R01 AA007535, K05 AA017688, P50 AA011998, R01 AA013326] Funding Source: Medline
- NIAMS NIH HHS [R21 AR056042, P60 AR047785, R01 AR056291] Funding Source: Medline
- NIA NIH HHS [R01 AG023629, N01AG12100, R01 AG027058, R01 AG018728, R01 AG015928, N01AG12109, R01 AG020098] Funding Source: Medline
- NIDA NIH HHS [R01 DA012854] Funding Source: Medline
- NIDDK NIH HHS [P30 DK063491, P30 DK079637, P30 DK072488, P60 DK079637] Funding Source: Medline
- NIGMS NIH HHS [U01 GM074518] Funding Source: Medline
- NIMH NIH HHS [R01 MH066206] Funding Source: Medline
- Wellcome Trust [090532] Funding Source: Medline
- Chief Scientist Office [CZB/4/710] Funding Source: Medline
- BBSRC [BB/F019394/1] Funding Source: UKRI
- MRC [MC_PC_U127527198, MC_PC_U127592696, MC_U127527198, MC_UU_12015/1, G0600237, G1002084, MR/K018647/1, G0700704, G9521010, MC_U127592696, MC_U106188470, MC_PC_U127561128] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish
- Cancer Research UK [14136, 12076] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [G9521010, MR/K026992/1, G1002084, MC_PC_13041, MC_UU_12015/1, MC_U106179471, MC_U106188470, MC_PC_U127527198, G0801056B, MC_PC_U127592696, G0401527, G0700704, MC_U127592696, MC_U127527198, MR/K006584/1, G1000143, MC_PC_U127561128, G0600237] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10113, NF-SI-0512-10114, NF-SI-0512-10052] Funding Source: researchfish
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Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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