{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:52:01Z","timestamp":1793638321069,"version":"4.5.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Several epidemiological studies have reported a possible correlation between risk of gout and metabolic disorders including type 2 diabetes, insulin resistance, obesity, dyslipidemia, and hypertension. However, it is unclear if this association is causal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used Mendelian randomization (MR) to evaluate the causal relation between metabolic conditions and gout or serum urate concentration by inverse-variance-weighted (conventional) and weighted median methods. Furthermore, MR-Egger regression and MR-pleiotropy residual sum and outlier (PRESSO) method were used to explore pleiotropy. Genetic instruments for metabolic disorders and outcome (gout and serum urate) were obtained from several genome-wide association studies on individuals of mainly European ancestry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Conventional MR analysis showed a robust causal association of increasing obesity measured by body mass index (BMI), high-density lipoprotein cholesterol (HDL), and systolic blood pressure (SBP) with risk of gout. A causal relationship between fasting insulin, BMI, HDL, triglycerides (TG), SBP, alanine aminotransferase (ALT), and serum urate was also observed. These results were consistent in weighted median method and MR-PRESSO after removing outliers identified. Our analysis also indicated that HDL and serum urate as well as gout have a bidirectional causal effect on each other.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study suggested causal effects between glycemic traits, obesity, dyslipidemia, blood pressure, liver function, and serum urate as well as gout, which implies that metabolic factors contribute to the development of gout\n                      <jats:italic>via<\/jats:italic>\n                      serum urate, as well as potential benefit of sound management of increased serum urate in patients with obesity, dyslipidemia, hypertension, and liver dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2022.917056","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T01:40:40Z","timestamp":1659663640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":61,"title":["The role of obesity, type 2 diabetes, and metabolic factors in gout: A Mendelian randomization study"],"prefix":"10.3389","volume":"13","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dide","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(09)60883-7","article-title":"Gout","volume":"375","author":"Richette","year":"2010","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.91","article-title":"Global epidemiology of gout: prevalence, incidence and risk factors","volume":"11","author":"Kuo","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(08)61343-4","article-title":"Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study","volume":"372","author":"Dehghan","year":"2008","journal-title":"Lancet (London England)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.107","article-title":"SLC2A9 influences uric acid concentrations with pronounced sex-specific effects","volume":"40","author":"D\u00f6ring","year":"2008","journal-title":"Nat Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)00346-9","article-title":"Gout","volume":"388","author":"Dalbeth","year":"2016","journal-title":"Lancet (London England)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/art.27338","article-title":"Epidemiology of gout in women: Fifty-two-year followup of a prospective cohort","volume":"62","author":"Bhole","year":"2010","journal-title":"Arthritis Rheum"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20479","article-title":"Obesity and younger age at gout onset in a community-based cohort","volume":"63","author":"DeMarco","year":"2011","journal-title":"Arthritis Care Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-98","article-title":"The prevalence of rheumatic diseases in central Greece: a population survey","volume":"11","author":"Anagnostopoulos","year":"2010","journal-title":"BMC Musculoskeletal Disord"},{"key":"B9","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12944-020-01211-z","article-title":"Hyperuricemia and its association with adiposity and dyslipidemia in Northwest China: results from cardiovascular risk survey in xinjiang (CRS 2008-2012)","volume":"19","author":"Liu","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-009-0031-9","article-title":"Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions","volume":"58","author":"Miao","year":"2009","journal-title":"Inflammation Res Off J Eur Histamine Res Soc [et al]"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21824","article-title":"Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: a prospective study","volume":"65","author":"Chen","year":"2013","journal-title":"Arthritis Care Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-015-9682-5","article-title":"Hyperuricemia and nonalcoholic fatty liver disease: from bedside to bench and back","volume":"10","author":"Xu","year":"2016","journal-title":"Hepatol Int"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0205-x","article-title":"Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits","volume":"50","author":"Evangelou","year":"2018","journal-title":"Nat Genet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1038\/s41467-021-22338-2","article-title":"Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes","volume":"12","author":"Pazoki","year":"2021","journal-title":"Nat Commun"},{"key":"B17","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/ng.2385","article-title":"Large-Scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways","volume":"44","author":"Scott","year":"2012","journal-title":"Nat Genet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature14132","article-title":"New genetic loci link adipose and insulin biology to body fat distribution","volume":"518","author":"Shungin","year":"2015","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1038\/s41467-018-04951-w","article-title":"Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes","volume":"9","author":"Xue","year":"2018","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels","volume":"45","author":"Willer","year":"2013","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2500","article-title":"Genome-wide association analyses identify 18 new loci associated with serum urate concentrations","volume":"45","author":"K\u00f6ttgen","year":"2013","journal-title":"Nat Genet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"The MR-base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1177\/0962280210394459","article-title":"Using multiple genetic variants as instrumental variables for modifiable risk factors","volume":"21","author":"Palmer","year":"2012","journal-title":"Stat Methods Med Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/jrsm.12","article-title":"A basic introduction to fixed-effect and random-effects models for meta-analysis","volume":"1","author":"Borenstein","year":"2010","journal-title":"Res Synth Methods"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/13548506.2019.1707241","article-title":"Gout and risk of diabetes mellitus: meta-analysis of observational studies","volume":"25","author":"Zhao","year":"2020","journal-title":"Psychol Health Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.130013","article-title":"Impact of diabetes against the future risk of developing gout","volume":"69","author":"Rodr\u00edguez","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/srep25766","article-title":"Bidirectional association between diabetes and gout: the Singapore Chinese health study","volume":"6","author":"Pan","year":"2016","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7326\/m19-2610","article-title":"Assessing the risk for gout with sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: A population-based cohort study","volume":"172","author":"Fralick","year":"2020","journal-title":"Ann Internal Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03470210076036","article-title":"Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration","volume":"266","author":"Facchini","year":"1991","journal-title":"Jama"},{"key":"B33","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s13075-018-1612-1","article-title":"Obesity, hypertension and diuretic use as risk factors for incident gout: a systematic review and meta-analysis of cohort studies","volume":"20","author":"Evans","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s13075-021-02497-9","article-title":"Risk of gout among Taiwanese adults with ALDH-2 rs671 polymorphism according to BMI and alcohol intake","volume":"23","author":"Liu","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B35","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1186\/s12967-019-02142-9","article-title":"Nonlinear relationship between serum uric acid and body mass index: a cross-sectional study of a general population in coastal China","volume":"17","author":"Zhou","year":"2019","journal-title":"J Trans Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key229","article-title":"Genetic association between adiposity and gout: a mendelian randomization study","volume":"57","author":"Larsson","year":"2018","journal-title":"Rheumatol (Oxford England)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12944-020-1197-y","article-title":"The comparison of dyslipidemia and serum uric acid in patients with gout and asymptomatic hyperuricemia: a cross-sectional study","volume":"19","author":"Liang","year":"2020","journal-title":"Lipids Health Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002937","article-title":"Genetically determined serum urate levels and cardiovascular and other diseases in UK biobank cohort: A phenome-wide mendelian randomization study","volume":"16","author":"Li","year":"2019","journal-title":"PloS Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1186\/s12967-020-02590-8","article-title":"Association of hypertension and hypertriglyceridemia on incident hyperuricemia: an 8-year prospective cohort study","volume":"18","author":"Zhang","year":"2020","journal-title":"J Trans Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185x.12689","article-title":"Central arterial characteristics of gout patients with chronic kidney diseases","volume":"20","author":"Celik","year":"2017","journal-title":"Int J Rheum Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.12659\/msm.895448","article-title":"Relationship between hyperuricemia and cardiovascular disease risk factors in a Chinese population: A cross-sectional study","volume":"21","author":"Su","year":"2015","journal-title":"Med Sci Monit Int Med J Exp Clin Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3109\/03009741003742797","article-title":"Gout and risk of non-alcoholic fatty liver disease","volume":"39","author":"Kuo","year":"2010","journal-title":"Scand J Rheumatol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.917056\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T01:40:50Z","timestamp":1659663650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.917056\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,5]]},"references-count":42,"alternative-id":["10.3389\/fendo.2022.917056"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.917056","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,5]]},"article-number":"917056"}}