Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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23263486
TITLE
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
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.
DATE PUBLISHED
2013 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/03/28
accepted 2012/11/27
aheadofprint 2012/12/23
entrez 2012/12/25 06:00
pubmed 2012/12/25 06:00
medline 2013/03/27 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Köttgen A Köttgen Anna A Renal Division, Freiburg University Hospital, Freiburg, Germany. anna.koettgen@uniklinik-freiburg.de
Albrecht E Albrecht Eva E
Teumer A Teumer Alexander A
Vitart V Vitart Veronique V
Krumsiek J Krumsiek Jan J
Hundertmark C Hundertmark Claudia C
Pistis G Pistis Giorgio G
Ruggiero D Ruggiero Daniela D
O'Seaghdha CM O'Seaghdha Conall M CM
Haller T Haller Toomas T
Yang Q Yang Qiong Q
Tanaka T Tanaka Toshiko T
Johnson AD Johnson Andrew D AD
Kutalik Z Kutalik Zoltán Z
Smith AV Smith Albert V AV
Shi J Shi Julia J
Struchalin M Struchalin Maksim M
Middelberg RP Middelberg Rita P S RP
Brown MJ Brown Morris J MJ
Gaffo AL Gaffo Angelo L AL
Pirastu N Pirastu Nicola N
Li G Li Guo G
Hayward C Hayward Caroline C
Zemunik T Zemunik Tatijana T
Huffman J Huffman Jennifer J
Yengo L Yengo Loic L
Zhao JH Zhao Jing Hua JH
Demirkan A Demirkan Ayse A
Feitosa MF Feitosa Mary F MF
Liu X Liu Xuan X
Malerba G Malerba Giovanni G
Lopez LM Lopez Lorna M LM
van der Harst P van der Harst Pim P
Li X Li Xinzhong X
Kleber ME Kleber Marcus E ME
Hicks AA Hicks Andrew A AA
Nolte IM Nolte Ilja M IM
Johansson A Johansson Asa A
Murgia F Murgia Federico F
Wild SH Wild Sarah H SH
Bakker SJ Bakker Stephan J L SJ
Peden JF Peden John F JF
Dehghan A Dehghan Abbas A
Steri M Steri Maristella M
Tenesa A Tenesa Albert A
Lagou V Lagou Vasiliki V
Salo P Salo Perttu P
Mangino M Mangino Massimo M
Rose LM Rose Lynda M LM
Lehtimäki T Lehtimäki Terho T
Woodward OM Woodward Owen M OM
Okada Y Okada Yukinori Y
Tin A Tin Adrienne A
Müller C Müller Christian C
Oldmeadow C Oldmeadow Christopher C
Putku M Putku Margus M
Czamara D Czamara Darina D
Kraft P Kraft Peter P
Frogheri L Frogheri Laura L
Thun GA Thun Gian Andri GA
Grotevendt A Grotevendt Anne A
Gislason GK Gislason Gauti Kjartan GK
Harris TB Harris Tamara B TB
Launer LJ Launer Lenore J LJ
McArdle P McArdle Patrick P
Shuldiner AR Shuldiner Alan R AR
Boerwinkle E Boerwinkle Eric E
Coresh J Coresh Josef J
Schmidt H Schmidt Helena H
Schallert M Schallert Michael M
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Kubo M Kubo Michiaki M
Nakamura Y Nakamura Yusuke Y
Tanaka T Tanaka Toshihiro T
Munroe PB Munroe Patricia B PB
Samani NJ Samani Nilesh J NJ
Jacobs DR Jr Jacobs David R DR
Liu K Liu Kiang K
D'Adamo P D'Adamo Pio P
Ulivi S Ulivi Sheila S
Rotter JI Rotter Jerome I JI
Psaty BM Psaty Bruce M BM
Vollenweider P Vollenweider Peter P
Waeber G Waeber Gerard G
Campbell S Campbell Susan S
Devuyst O Devuyst Olivier O
Navarro P Navarro Pau P
Kolcic I Kolcic Ivana I
Hastie N Hastie Nicholas N
Balkau B Balkau Beverley B
Froguel P Froguel Philippe P
Esko T Esko Tõnu T
Salumets A Salumets Andres A
Khaw KT Khaw Kay Tee KT
Langenberg C Langenberg Claudia C
Wareham NJ Wareham Nicholas J NJ
Isaacs A Isaacs Aaron A
Kraja A Kraja Aldi A
Zhang Q Zhang Qunyuan Q
Wild PS Wild Philipp S PS
Scott RJ Scott Rodney J RJ
Holliday EG Holliday Elizabeth G EG
Org E Org Elin E
Viigimaa M Viigimaa Margus M
Bandinelli S Bandinelli Stefania S
Metter JE Metter Jeffrey E JE
Lupo A Lupo Antonio A
Trabetti E Trabetti Elisabetta E
Sorice R Sorice Rossella R
Döring A Döring Angela A
Lattka E Lattka Eva E
Strauch K Strauch Konstantin K
Theis F Theis Fabian F
Waldenberger M Waldenberger Melanie M
Wichmann HE Wichmann H-Erich HE
Davies G Davies Gail G
Gow AJ Gow Alan J AJ
Bruinenberg M Bruinenberg Marcel M
LifeLines Cohort Study
Stolk RP Stolk Ronald P RP
Kooner JS Kooner Jaspal S JS
Zhang W Zhang Weihua W
Winkelmann BR Winkelmann Bernhard R BR
Boehm BO Boehm Bernhard O BO
Lucae S Lucae Susanne S
Penninx BW Penninx Brenda W BW
Smit JH Smit Johannes H JH
Curhan G Curhan Gary G
Mudgal P Mudgal Poorva P
Plenge RM Plenge Robert M RM
Portas L Portas Laura L
Persico I Persico Ivana I
Kirin M Kirin Mirna M
Wilson JF Wilson James F JF
Mateo Leach I Mateo Leach Irene I
van Gilst WH van Gilst Wiek H WH
Goel A Goel Anuj A
Ongen H Ongen Halit H
Hofman A Hofman Albert A
Rivadeneira F Rivadeneira Fernando F
Uitterlinden AG Uitterlinden Andre G AG
Imboden M Imboden Medea M
von Eckardstein A von Eckardstein Arnold A
Cucca F Cucca Francesco F
Nagaraja R Nagaraja Ramaiah R
Piras MG Piras Maria Grazia MG
Nauck M Nauck Matthias M
Schurmann C Schurmann Claudia C
Budde K Budde Kathrin K
Ernst F Ernst Florian F
Farrington SM Farrington Susan M SM
Theodoratou E Theodoratou Evropi E
Prokopenko I Prokopenko Inga I
Stumvoll M Stumvoll Michael M
Jula A Jula Antti A
Perola M Perola Markus M
Salomaa V Salomaa Veikko V
Shin SY Shin So-Youn SY
Spector TD Spector Tim D TD
Sala C Sala Cinzia C
Ridker PM Ridker Paul M PM
Kähönen M Kähönen Mika M
Viikari J Viikari Jorma J
Hengstenberg C Hengstenberg Christian C
Nelson CP Nelson Christopher P CP
CARDIoGRAM Consortium
DIAGRAM Consortium
ICBP Consortium
MAGIC Consortium
Meschia JF Meschia James F JF
Nalls MA Nalls Michael A MA
Sharma P Sharma Pankaj P
Singleton AB Singleton Andrew B AB
Kamatani N Kamatani Naoyuki N
Zeller T Zeller Tanja T
Burnier M Burnier Michel M
Attia J Attia John J
Laan M Laan Maris M
Klopp N Klopp Norman N
Hillege HL Hillege Hans L HL
Kloiber S Kloiber Stefan S
Choi H Choi Hyon H
Pirastu M Pirastu Mario M
Tore S Tore Silvia S
Probst-Hensch NM Probst-Hensch Nicole M NM
Völzke H Völzke Henry H
Gudnason V Gudnason Vilmundur V
Parsa A Parsa Afshin A
Schmidt R Schmidt Reinhold R
Whitfield JB Whitfield John B JB
Fornage M Fornage Myriam M
Gasparini P Gasparini Paolo P
Siscovick DS Siscovick David S DS
Polašek O Polašek Ozren O
Campbell H Campbell Harry H
Rudan I Rudan Igor I
Bouatia-Naji N Bouatia-Naji Nabila N
Metspalu A Metspalu Andres A
Loos RJ Loos Ruth J F RJ
van Duijn CM van Duijn Cornelia M CM
Borecki IB Borecki Ingrid B IB
Ferrucci L Ferrucci Luigi L
Gambaro G Gambaro Giovanni G
Deary IJ Deary Ian J IJ
Wolffenbuttel BH Wolffenbuttel Bruce H R BH
Chambers JC Chambers John C JC
März W März Winfried W
Pramstaller PP Pramstaller Peter P PP
Snieder H Snieder Harold H
Gyllensten U Gyllensten Ulf U
Wright AF Wright Alan F AF
Navis G Navis Gerjan G
Watkins H Watkins Hugh H
Witteman JC Witteman Jacqueline C M JC
Sanna S Sanna Serena S
Schipf S Schipf Sabine S
Dunlop MG Dunlop Malcolm G MG
Tönjes A Tönjes Anke A
Ripatti S Ripatti Samuli S
Soranzo N Soranzo Nicole N
Toniolo D Toniolo Daniela D
Chasman DI Chasman Daniel I DI
Raitakari O Raitakari Olli O
Kao WH Kao W H Linda WH
Ciullo M Ciullo Marina M
Fox CS Fox Caroline S CS
Caulfield M Caulfield Mark M
Bochud M Bochud Murielle M
Gieger C Gieger Christian C
INVESTIGATORS
JOURNAL
VOLUME: 45
ISSUE: 2
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2013
MONTH: Feb
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
12076 Cancer Research UK United Kingdom
14136 Cancer Research UK United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
CZB/4/710 Chief Scientist Office United Kingdom
G0600237 Medical Research Council United Kingdom
G0700704 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
G1002084 Medical Research Council United Kingdom
G9521010 Medical Research Council United Kingdom
HHSN268201100005C NHLBI NIH HHS United States
HHSN268201100006C NHLBI NIH HHS United States
HHSN268201100007C NHLBI NIH HHS United States
HHSN268201100008C NHLBI NIH HHS United States
HHSN268201100009C NHLBI NIH HHS United States
HHSN268201100010C NHLBI NIH HHS United States
HHSN268201100011C NHLBI NIH HHS United States
HHSN268201100012C NHLBI NIH HHS United States
HHSN268201200036C NHLBI NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
K12 RR023250 NCRR NIH HHS United States
M01 RR016500 NCRR NIH HHS United States
MC_PC_U127561128 Medical Research Council United Kingdom
MC_U106179471 Medical Research Council United Kingdom
MC_U106188470 Medical Research Council United Kingdom
MC_U127527198 Medical Research Council United Kingdom
MC_U127592696 Medical Research Council United Kingdom
MR/K006584/1 Medical Research Council United Kingdom
MR/K026992/1 Medical Research Council United Kingdom
N01 HC025195 NHLBI NIH HHS United States
N01 HC045134 NHLBI NIH HHS United States
N01 HC095170 NHLBI NIH HHS United States
N01 HC095171 NHLBI NIH HHS United States
N01 HC095172 NHLBI NIH HHS United States
N01AG12100 NIA NIH HHS United States
N01AG12109 NIA NIH HHS United States
N01HC05187 NHLBI NIH HHS United States
N01HC45204 NHLBI NIH HHS United States
N01HC45205 NHLBI NIH HHS United States
N01HC48047 NHLBI NIH HHS United States
N01HC48048 NHLBI NIH HHS United States
N01HC48049 NHLBI NIH HHS United States
N01HC48050 NHLBI NIH HHS United States
N01HC55222 NHLBI NIH HHS United States
N01HC75150 NHLBI NIH HHS United States
N01HC85079 NHLBI NIH HHS United States
N01HC85086 NHLBI NIH HHS United States
N01HC95095 NHLBI NIH HHS United States
N02HL64278 NHLBI NIH HHS United States
P01 CA087969 NCI NIH HHS United States
P30 DK063491 NIDDK NIH HHS United States
P30 DK072488 NIDDK NIH HHS United States
P30 DK079637 NIDDK NIH HHS United States
P50 AA011998 NIAAA NIH HHS United States
P60 AR047785 NIAMS NIH HHS United States
P60 DK079637 NIDDK NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
R01 AG015928 NIA NIH HHS United States
R01 AG018728 NIA NIH HHS United States
R01 AG020098 NIA NIH HHS United States
R01 AG023629 NIA NIH HHS United States
R01 AG027058 NIA NIH HHS United States
R01 AR056291 NIAMS NIH HHS United States
R01 CA047988 NCI NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 HL043851 NHLBI NIH HHS United States
R01 HL059367 NHLBI NIH HHS United States
R01 HL080295 NHLBI NIH HHS United States
R01 HL084099 NHLBI NIH HHS United States
R01 HL086694 NHLBI NIH HHS United States
R01 HL087641 NHLBI NIH HHS United States
R01 HL087652 NHLBI NIH HHS United States
R01 HL088119 NHLBI NIH HHS United States
R01 HL105756 NHLBI NIH HHS United States
R01 MH066206 NIMH NIH HHS United States
R21 AR056042 NIAMS NIH HHS United States
U01 GM074518 NIGMS NIH HHS United States
U01 HG004402 NHGRI NIH HHS United States
U01 HG004424 NHGRI NIH HHS United States
U01 HG004446 NHGRI NIH HHS United States
U01 HG004729 NHGRI NIH HHS United States
U01 HL069757 NHLBI NIH HHS United States
U01 HL072515 NHLBI NIH HHS United States
U01 HL084756 NHLBI NIH HHS United States
UL1 RR025005 NCRR NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
Z01 AG000954-06 Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Analysis of Variance
European Continental Ancestry Group
Gene Frequency
Genetic Loci genetics
Genome-Wide Association Study genetics
Glucose metabolism
Gout genetics
Humans genetics
Inhibins metabolism
Polymorphism, Single Nucleotide genetics
Signal Transduction genetics
Uric Acid blood
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
268B43MJ25 Uric Acid
57285-09-3 Inhibins
IY9XDZ35W2 Glucose
OTHER ID's
OTHERID SOURCE
NIHMS458823 NLM
PMC3663712 NLM