Pulse lineResearch With Heart Logo

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

TitleGenome-wide association analyses identify 18 new loci associated with serum urate concentrations.
Publication TypeJournal Article
Year of Publication2013
AuthorsKöttgen A, Albrecht E, Teumer A, et al.
Secondary AuthorsGieger C
Corporate AuthorsLifeLines Cohort Study, CARDIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium
JournalNat Genet
Volume45
Issue2
Pagination145-54
Date Published2013 Feb
ISSN1546-1718
KeywordsAnalysis of Variance, European Continental Ancestry Group, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Glucose, Gout, Humans, Inhibins, Polymorphism, Single Nucleotide, Signal Transduction, Uric Acid
Abstract

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, SFMBT1, 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.

DOI10.1038/ng.2500
Alternate JournalNat Genet
PubMed ID23263486
PubMed Central IDPMC3663712
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
R01 AA007535 / AA / NIAAA NIH HHS / United States
K12 RR023250 / RR / NCRR NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
N01 HC095170 / HC / NHLBI NIH HHS / United States
R01 AA014041 / AA / NIAAA NIH HHS / United States
K05 AA017688 / AA / NIAAA NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
R01 MH066206 / MH / NIMH NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
P50 AA011998 / AA / NIAAA NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
R01 HL043851 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
12076 / / Cancer Research UK / United Kingdom
N01 HC025195 / HC / NHLBI NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 AA013326 / AA / NIAAA NIH HHS / United States
G1000143 / / Medical Research Council / United Kingdom
N01 HC095172 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
P60 AR047785 / AR / NIAMS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
N02HL64278 / HL / NHLBI NIH HHS / United States
N01 HC095171 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_U127527198 / / Medical Research Council / United Kingdom
R01 AA013321 / AA / NIAAA NIH HHS / United States
MC_U106179471 / / Medical Research Council / United Kingdom
U01 HL084756 / HL / NHLBI NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
14136 / / Cancer Research UK / United Kingdom
N01HC95095 / HL / NHLBI NIH HHS / United States
G1002084 / / Medical Research Council / United Kingdom
MC_PC_U127592696 / / Medical Research Council / United Kingdom
G0401527 / / Medical Research Council / United Kingdom
R01 AR056291 / AR / NIAMS NIH HHS / United States
P60 DK079637 / DK / NIDDK NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
R01 HL084099 / HL / NHLBI NIH HHS / United States
N01 HC045134 / HC / NHLBI NIH HHS / United States
MC_PC_U127561128 / / Medical Research Council / United Kingdom
U01 HL072515 / HL / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R21 AR056042 / AR / NIAMS NIH HHS / United States
M01 RR016500 / RR / NCRR NIH HHS / United States
R01 DA012854 / DA / NIDA NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
N01AG12109 / AG / NIA NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC05187 / HL / NHLBI NIH HHS / United States
MR/K006584/1 / / Medical Research Council / United Kingdom
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
G0700704 / / Medical Research Council / United Kingdom
N01HC45204 / HL / NHLBI NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_U127592696 / / Medical Research Council / United Kingdom
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
Z01 AG000954-06 / / Intramural NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
MC_U106188470 / / Medical Research Council / United Kingdom
G0600237 / / Medical Research Council / United Kingdom
U01 HL069757 / HL / NHLBI NIH HHS / United States
R01 AG018728 / AG / NIA NIH HHS / United States
U01 GM074518 / GM / NIGMS NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States
R01 AA013320 / AA / NIAAA NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States