Journal
PLOS ONE
Volume 10, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0119752
Keywords
-
Categories
Funding
- NIH [N01-AG-12100]
- NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, UL1RR025005]
- Emmy Noether Programme of the German Research Foundation [KO3598/2-1]
- NIH Roadmap for Medical Research
- Intramural Research Program of the NIH, National Institute on Aging
- MedStar Research Institute
- Medical Research Council of Great Britain [G9521010D]
- Wellcome Trust as part of the Wellcome Trust Case Control Consortium
- GlaxoSmithKline
- Faculty of Biology and Medicine of Lausanne
- Swiss National Science Foundation [33CSCO-122661]
- Medical Research Council (UK)
- Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]
- EU framework 6 project EUROSPAN [LSHG-CT-2006-018947]
- EUROSPAN (European Special Populations Research Network)
- European Commission FP6 STRP grant [LSHG-CT-2006-018947, 018947]
- Netherlands Organisation for Scientific Research [047.016.009, 047.017.043]
- Erasmus MC
- Centre for Medical Systems Biology (CMSB, National Genomics Initiative)
- Netherlands Brain Foundation (HersenStichting Nederland)
- EU FP7 grant BBMRI-LPC [313010]
- Estonian Government [IUT20-60, IUT24-6]
- Estonian Research Roadmap through the Estonian Ministry of Education and Research [3.2.0304.11-0312]
- Center of Excellence in Genomics (EXCEGEN)
- University of Tartu
- EFSD New Horizons grant
- National institute for Health and Welfare
- Finnish Centre for Pensions
- Social Insurance Institution of Finland (KELA)
- The Local Government Pensions Institution (KEVA)
- Wellcome Trust Sanger Institute
- Academy of Finland [129494, 139635]
- Italian Ministry of Health [ICS110.1/RF97.71]
- U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]
- EU [Vasoplus-037254]
- Italian Ministry of Universities [FIRB -RBIN064YAT]
- Assessorato Ricerca Regione Campania
- Ente Parco Nazionale del Cilento e Vallo di Diano
- Fondazione Banco di Napoli
- Regione FVG [L.26.2008]
- Compagnia di San Paolo, Torino, Italy
- Cariplo Fundation, Milano, Italy
- Italian Ministry of Health Progetto Finalizzato
- project on Preventive Medicine
- Prin
- Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
- German Federal Ministry of Education and Research (BMBF)
- German National Genome Research Network (NGFN)
- Munich Center of Health Sciences (MC Health) as part of LMUinnovativ
- Age UK (The Disconnected Mind project)
- BBSRC
- Medical Research Council (MRC)
- Ministry of Health
- Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano
- South Tyrolean Sparkasse Foundation
- Geestkracht programme of the Dutch Scientific Organization (ZON-MW) [10-000-1002]
- Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health
- Netherlands Scientific Organization [I 480-05-003]
- Swedish Medical Research Council [K2007-66X-20270-01-3]
- Foundation for Strategic Research (SSF)
- European Commission [01947, LSHG-CT-2006-01947]
- Swedish Society for Medical Research
- Italian Ministry of Education, University and Research (MIUR) [5571/DSPAR/2002, 718/Ric/2005]
- Chief Scientist Office of the Scottish Government
- Royal Society
- Medical Research Council Human Genetics Unit
- European Union framework program 6 EUROSPAN project [LSHG-CT-2006-018947]
- EC Sixth Framework Programme [LSHM-CT-2007-037273]
- Aztrazenneca AB
- Wellcome Trust core grant award [075491/Z/04]
- Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03012]
- Research Institute for Diseases in the Elderly [014-93-015]
- Netherlands Genomics Initiative (NGI)/ Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- network 'Greifswald Approach to Individualized Medicine (GANI_MED)' by Federal Ministry of Education and Research [03IS2061A]
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg - West Pomerania
- Cancer Research UK [C348/A12076, C348/A6361]
- Centre Grant from CORE as part of the Digestive Cancer Campaign
- Wellcome Trust
- European Community's Seventh Framework Programme
- National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London
- ERC Advanced Principal Investigator award
- New Zealand Health Research Council
- Biotechnology and Biological Sciences Research Council [BB/F019394/1, BB/K000195/1] Funding Source: researchfish
- Cancer Research UK [12076] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [MR/K018647/1, MC_PC_U127592696, G0700704, MC_PC_U127527198, G9521010, MR/K026992/1, MR/K006584/1, MC_PC_U127561128] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10113] Funding Source: researchfish
- BBSRC [BB/K000195/1, BB/F019394/1] Funding Source: UKRI
- MRC [MC_PC_U127527198, MC_PC_U127561128, MR/K018647/1, G0700704, G9521010, MC_PC_U127592696] Funding Source: UKRI
Ask authors/readers for more resources
We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
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