TY - JOUR
T1 - Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
AU - LifeLines Cohort Study
AU - Köttgen, Anna
AU - Albrecht, Eva
AU - Teumer, Alexander
AU - Vitart, Veronique
AU - Krumsiek, Jan
AU - Hundertmark, Claudia
AU - Pistis, Giorgio
AU - Ruggiero, Daniela
AU - O'Seaghdha, Conall M
AU - Haller, Toomas
AU - Yang, Qiong
AU - Tanaka, Toshiko
AU - Johnson, Andrew D
AU - Kutalik, Zoltán
AU - Smith, Albert V
AU - Shi, Julia
AU - Struchalin, Maksim
AU - Middelberg, Rita P S
AU - Brown, Morris J
AU - Gaffo, Angelo L
AU - Pirastu, Nicola
AU - Li, Guo
AU - Hayward, Caroline
AU - Zemunik, Tatijana
AU - Huffman, Jennifer
AU - Yengo, Loic
AU - Zhao, Jing Hua
AU - Demirkan, Ayse
AU - Feitosa, Mary F
AU - Liu, Xuan
AU - Malerba, Giovanni
AU - Lopez, Lorna M
AU - van der Harst, Pim
AU - Li, Xinzhong
AU - Kleber, Marcus E
AU - Wild, Sarah H
AU - Tenesa, Albert
AU - Navarro, Pau
AU - Hastie, Nicholas
AU - Davies, Gail
AU - Gow, Alan J
AU - Wilson, James F
AU - Farrington, Susan M
AU - Theodoratou, Evropi
AU - Polasek, Ozren
AU - Campbell, Harry
AU - Rudan, Igor
AU - Deary, Ian J
AU - Wright, Alan F
AU - Dunlop, Malcolm G
N1 - The whole genome association study was funded by the Biotechnology
and Biological Sciences Research Council (BBSRC) (Ref. BB/F019394/1). The LBC1936 data collection was funded by Research Into Ageing (Ref. 251). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (Ref. G0700704/84698). Funding from the BBSRC, Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC) and Medical Research Council (MRC) is gratefully acknowledged.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
U2 - 10.1038/ng.2500
DO - 10.1038/ng.2500
M3 - Article
C2 - 23263486
SN - 1546-1718
VL - 45
SP - 145
EP - 154
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -