To further identify genetic variants associated with serum urate concentrations and gout, several additional analyses were carried out. These included X-chromosome analyses, sex-stratified analyses, a gene-based test and urate transporter candidate analyses, as well as secondary analyses to improve the characterization of associated SNPs. To this end, we investigated associations with FEUA, associations in individuals of non-European ancestry, associations with transcript expression, associations with serum metabolite concentrations, risk score analyses and associations with other urate-related phenotypes. Secondary analyses are described in detail in the Supplementary Note. As a result of the secondary analyses, seven additional SNPs were identified for further replication testing: one from the analysis in men only, five from the analysis in women and one from the urate transporter candidate analysis. A new part of the secondary analyses was the implementation of functional association networks as described in the Supplementary Note. As detailed there, the approach based on functional associations among the urate genes, mostly protein-protein interactions, led to the identification of 17 additional independent SNPs in newly identified genomic regions that were subjected to replication testing. Altogether, we therefore tested 61 SNPs (37 overall, 6 sex specific, 1 urate transporter candidate and 17 network) for replication in additional study samples.
Partial Protocol Preview
This section provides a glimpse into the protocol. The remaining content is hidden due to licensing restrictions, but the full text is available at the following link:
Access Free Full Text.
Köttgen A., Albrecht E., Teumer A., Vitart V., Krumsiek J., Hundertmark C., Pistis G., Ruggiero D., O’Seaghdha C.M., Haller T., Yang Q., Tanaka T., Johnson A.D., Kutalik Z., Smith A.V., Shi J., Struchalin M., Middelberg R.P., Brown M.J., Gaffo A.L., Pirastu N., Li G., Hayward C., Zemunik T., Huffman J., Yengo L., Zhao J.H., Demirkan A., Feitosa M.F., Liu X., Malerba G., Lopez L.M., van der Harst P., Li X., Kleber M.E., Hicks A.A., Nolte I.M., Johansson A., Murgia F., Wild S.H., Bakker S.J., Peden J.F., Dehghan A., Steri M., Tenesa A., Lagou V., Salo P., Mangino M., Rose L.M., Lehtimäki T., Woodward O.M., Okada Y., Tin A., Müller C., Oldmeadow C., Putku M., Czamara D., Kraft P., Frogheri L., Thun G.A., Grotevendt A., Gislason G.K., Harris T.B., Launer L.J., McArdle P., Shuldiner A.R., Boerwinkle E., Coresh J., Schmidt H., Schallert M., Martin N.G., Montgomery G.W., Kubo M., Nakamura Y., Tanaka T., Munroe P.B., Samani N.J., Jacobs DR J.r., Liu K., D’Adamo P., Ulivi S., Rotter J.I., Psaty B.M., Vollenweider P., Waeber G., Campbell S., Devuyst O., Navarro P., Kolcic I., Hastie N., Balkau B., Froguel P., Esko T., Salumets A., Khaw K.T., Langenberg C., Wareham N.J., Isaacs A., Kraja A., Zhang Q., Wild P.S., Scott R.J., Holliday E.G., Org E., Viigimaa M., Bandinelli S., Metter J.E., Lupo A., Trabetti E., Sorice R., Döring A., Lattka E., Strauch K., Theis F., Waldenberger M., Wichmann H.E., Davies G., Gow A.J., Bruinenberg M., Study L.C., Stolk R.P., Kooner J.S., Zhang W., Winkelmann B.R., Boehm B.O., Lucae S., Penninx B.W., Smit J.H., Curhan G., Mudgal P., Plenge R.M., Portas L., Persico I., Kirin M., Wilson J.F., Leach I.M., van Gilst W.H., Goel A., Ongen H., Hofman A., Rivadeneira F., Uitterlinden A.G., Imboden M., von Eckardstein A., Cucca F., Nagaraja R., Piras M.G., Nauck M., Schurmann C., Budde K., Ernst F., Farrington S.M., Theodoratou E., Prokopenko I., Stumvoll M., Jula A., Perola M., Salomaa V., Shin S.Y., Spector T.D., Sala C., Ridker P.M., Kähönen M., Viikari J., Hengstenberg C., Nelson C.P., Consortium C., Consortium D., Consortium I., Consortium M., Meschia J.F., Nalls M.A., Sharma P., Singleton A.B., Kamatani N., Zeller T., Burnier M., Attia J., Laan M., Klopp N., Hillege H.L., Kloiber S., Choi H., Pirastu M., Tore S., Probst-Hensch N.M., Völzke H., Gudnason V., Parsa A., Schmidt R., Whitfield J.B., Fornage M., Gasparini P., Siscovick D.S., Polašek O., Campbell H., Rudan I., Bouatia-Naji N., Metspalu A., Loos R.J., van Duijn C.M., Borecki I.B., Ferrucci L., Gambaro G., Deary I.J., Wolffenbuttel B.H., Chambers J.C., März W., Pramstaller P.P., Snieder H., Gyllensten U., Wright A.F., Navis G., Watkins H., Witteman J.C., Sanna S., Schipf S., Dunlop M.G., Tönjes A., Ripatti S., Soranzo N., Toniolo D., Chasman D.I., Raitakari O., Kao W.H., Ciullo M., Fox C.S., Caulfield M., Bochud M, & Gieger C. (2012). Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature genetics, 45(2), 145-154.
Publication 2012
European Gene testGenes Genetic variants GenomicGout Phenotypes Protein ReplicationSerum SnpsUrate Urate transporter WomenX chromosome
Corresponding Organization : Institute of Social and Preventive Medicine
Other organizations :
University Medical Center Freiburg, Helmholtz Zentrum München, Universität Greifswald, Institute of Bioinformatics and Systems Biology, Institute of Genetics and Biophysics, Framingham Heart Study, National Heart Lung and Blood Institute, University of Tartu, National Institute on Aging, University of Lausanne, Icelandic Heart Association, University of Maryland, Baltimore, Erasmus MC, Prince Charles Hospital, University of Cambridge, University of Alabama at Birmingham, Istituti di Ricovero e Cura a Carattere Scientifico, University of Trieste, University of Washington, University of Split, Institut Pasteur de Lille, Centre National de la Recherche Scientifique, MRC Epidemiology Unit, Addenbrooke's Hospital, Washington University in St. Louis, Boston University, University of Verona, University Medical Center Groningen, University of Groningen, Imperial College London, Eurac Research, Uppsala University Hospital, Wellcome Centre for Human Genetics, University of Oxford, Institute of Genetic and Biomedical Research, Oxford Centre for Diabetes, Endocrinology and Metabolism, Finnish Institute for Health and Welfare, St Thomas' Hospital, King's College London, Brigham and Women's Hospital, Fimlab (Finland), Tampere University, Tampere University Hospital, Johns Hopkins Medicine, Johns Hopkins University, RIKEN Center for Integrative Medical Sciences, Universität Hamburg, University Medical Center Hamburg-Eppendorf, University of Newcastle Australia, Max Planck Institute of Psychiatry, Harvard University, Swiss Tropical and Public Health Institute, Universitätsmedizin Greifswald, The University of Texas Health Science Center at Houston, Medical University of Graz, QIMR Berghofer Medical Research Institute, Queen Mary University of London, William Harvey Research Institute, Glenfield Hospital, National Institute for Health Research, University of Minnesota, Northwestern University, IRCCS Materno Infantile Burlo Garofolo, Cedars-Sinai Medical Center, Swiss Integrative Center for Human Health, University of Zurich, University Medical Center of the Johannes Gutenberg University Mainz, Johannes Gutenberg University Mainz, Tallinn University of Technology, Azienda Sanitaria di Firenze, Hammersmith Hospital, Ealing Hospital, University Hospital Ulm, EMGO Institute for Health and Care Research, Netherlands Consortium for Healthy Ageing, University Hospital of Zurich, Leipzig University, Wellcome Sanger Institute, Turku University Hospital, University of Turku, University Hospital Regensburg, Mayo Clinic in Florida, National Institutes of Health, University of Iceland, Agostino Gemelli University Polyclinic, University of Mannheim, Heidelberg University, University Hospital Heidelberg, Uppsala University, Istituto di Genetica Molecolare
Genetic variants associated with serum urate concentrations and gout
Sex-stratified analyses
Urate transporter candidate analyses
Functional association networks among urate genes
dependent variables
Serum urate concentrations
Fractional excretion of uric acid (FEUA)
Transcript expression
Serum metabolite concentrations
Other urate-related phenotypes
control variables
Individuals of non-European ancestry
controls
No positive or negative controls were explicitly mentioned in the input text.
Annotations
Based on most similar protocols
Etiam vel ipsum. Morbi facilisis vestibulum nisl. Praesent cursus laoreet felis. Integer adipiscing pretium orci. Nulla facilisi. Quisque posuere bibendum purus. Nulla quam mauris, cursus eget, convallis ac, molestie non, enim. Aliquam congue. Quisque sagittis nonummy sapien. Proin molestie sem vitae urna. Maecenas lorem.
As authors may omit details in methods from publication, our AI will look for missing critical information across the 5 most similar protocols.
About PubCompare
Our mission is to provide scientists with the largest repository of trustworthy protocols and intelligent analytical tools, thereby offering them extensive information to design robust protocols aimed at minimizing the risk of failures.
We believe that the most crucial aspect is to grant scientists access to a wide range of reliable sources and new useful tools that surpass human capabilities.
However, we trust in allowing scientists to determine how to construct their own protocols based on this information, as they are the experts in their field.
Ready to
get started?
Sign up for free.
Registration takes 20 seconds.
Available from any computer
No download required