{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:10:11Z","timestamp":1778163011118,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004906","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["PRCPGM-May25\/100001"],"award-info":[{"award-number":["PRCPGM-May25\/100001"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18281\/A29019"],"award-info":[{"award-number":["C18281\/A29019"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18281\/A29019"],"award-info":[{"award-number":["C18281\/A29019"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18281\/A29019"],"award-info":[{"award-number":["C18281\/A29019"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000321","name":"World Cancer Research Fund","doi-asserted-by":"publisher","award":["IIG_2019_1995"],"award-info":[{"award-number":["IIG_2019_1995"]}],"id":[{"id":"10.13039\/501100000321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000321","name":"World Cancer Research Fund","doi-asserted-by":"publisher","award":["IIG_2019_1995"],"award-info":[{"award-number":["IIG_2019_1995"]}],"id":[{"id":"10.13039\/501100000321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00c3\u00a4kares\u00c3\u00a4llskapet","doi-asserted-by":"publisher","award":["SLS-960379"],"award-info":[{"award-number":["SLS-960379"]}],"id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009336","name":"Bengt Ihres Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00032\/1"],"award-info":[{"award-number":["MC_UU_00032\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR202411"],"award-info":[{"award-number":["NIHR202411"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015250","name":"NIHR Bristol Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC-1215-20011"],"award-info":[{"award-number":["BRC-1215-20011"]}],"id":[{"id":"10.13039\/100015250","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004885","name":"Ume\u00c3\u00a5 Universitet","doi-asserted-by":"publisher","award":["FS 2.1.6-59-23"],"award-info":[{"award-number":["FS 2.1.6-59-23"]}],"id":[{"id":"10.13039\/501100004885","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Svensk-Franska Stiftelsen","award":["F0025_230413"],"award-info":[{"award-number":["F0025_230413"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Excess body adiposity is an established cause of renal cancer, but underlying molecular pathways mediating this relationship remain unclear. This study aimed to systematically evaluate a panel of obesity-related risk factors as potential mediators in renal cancer etiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      We used two complementary approaches to evaluate obesity-related risk factors in renal cancer etiology: (i) direct risk factor assessment in longitudinal cohorts and (ii) genetically proxied risk factors through two-sample Mendelian randomization (MR). Direct risk-factor association-analyses (i.e., cohort analyses) were based on the UK Biobank cohort study (472,337 cohort participants, including 1,382 incident renal cancer cases diagnosed during 5,586,414 person years of follow-up) and the Northern Sweden Health and Disease Study (NSHDS) for fasting insulin (204 pairs of cases and controls, ongoing recruitment and follow-up since 1985). We used Cox proportional hazards regression models to evaluate the association between risk factors and renal cancer risk with adjustment for age, sex, center of recruitment, education, smoking and alcohol drinking status. Two-sample MR analyses were based on a genome-wide association study (GWAS) of renal cancer (27,213 cases, 486,846 controls). We used the inverse-variance weighted (IVW) approach to estimate the association between risk factors and renal cancer risk. Mediation analyses were performed for traits displaying directionally consistent associations with renal cancer risk in both the cohort and MR analyses using the product method. We found consistent positive associations with renal cancer risk for fasting insulin (odds ratio per standard deviation increment [OR\n                      <jats:sub>MR<\/jats:sub>\n                      ]: 2.24, 95% confidence interval [95% CI]: 1.19, 4.22;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01; hazard ratio per standard deviation increment [HR\n                      <jats:sub>cohort<\/jats:sub>\n                      ]: 1.43, 95% CI: 1.02, 2.00;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04), triglycerides (OR\n                      <jats:sub>MR<\/jats:sub>\n                      : 1.11, 95% CI: 1.05, 1.17;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, HR\n                      <jats:sub>cohort<\/jats:sub>\n                      : 1.23, 95% CI: 1.11, 1.38;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), diastolic blood pressure (DBP) (OR\n                      <jats:sub>MR<\/jats:sub>\n                      : 1.14, 95% CI: 1.04, 1.26;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, HR\n                      <jats:sub>cohort<\/jats:sub>\n                      : 1.11, 95% CI: 1.05, 1.17;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and consistent inverse associations with renal cancer risk for sex-hormone binding globulin (SHBG) (OR\n                      <jats:sub>MR<\/jats:sub>\n                      : 0.80, 95% CI: 0.70, 0.90;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, HR\n                      <jats:sub>cohort<\/jats:sub>\n                      : 0.67, 95% CI: 0.58, 0.76;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and high-density lipoprotein (HDL) cholesterol (OR\n                      <jats:sub>MR<\/jats:sub>\n                      : 0.93, 95% CI: 0.88, 0.98;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, HR\n                      <jats:sub>cohort<\/jats:sub>\n                      : 0.72, 95% CI: 0.66, 0.77;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The main limitation of this study was that we had limited statistical power to evaluate some risk factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study highlights roles for fasting insulin, HDL cholesterol, DBP, triglycerides and SHBG in mediating the relationship between body adiposity and renal cancer risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004906","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:39:08Z","timestamp":1770748748000},"page":"e1004906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systematic assessment of obesity-related risk factors in renal cancer etiology: A longitudinal risk and Mendelian randomization analysis"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-9880","authenticated-orcid":true,"given":"Karine","family":"Alcala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-1419","authenticated-orcid":true,"given":"Daniela","family":"Mariosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-1970","authenticated-orcid":true,"given":"Sara","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9443-2119","authenticated-orcid":true,"given":"Claudia","family":"Coscia-Requena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1678-9328","authenticated-orcid":true,"given":"Niki","family":"Dimou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oskar","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-8314","authenticated-orcid":true,"given":"George Davey","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc J.","family":"Gunter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Pollak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Langdon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3116-5081","authenticated-orcid":true,"given":"Mattias","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"issue":"36","key":"pmed.1004906.ref001","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2018.79.1905","article-title":"Epidemiology and risk factors for kidney cancer","volume":"36","author":"G Scelo","year":"2018","journal-title":"J Clin Oncol"},{"issue":"3","key":"pmed.1004906.ref002","doi-asserted-by":"crossref","first-page":"79","DOI":"10.14740\/wjon1279","article-title":"Epidemiology of renal cell carcinoma","volume":"11","author":"SA Padala","year":"2020","journal-title":"World J Oncol"},{"issue":"1","key":"pmed.1004906.ref003","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1470-2045(14)71123-4","article-title":"Global burden of cancer attributable to high body-mass index in 2012: a population-based study","volume":"16","author":"M Arnold","year":"2015","journal-title":"Lancet Oncol"},{"issue":"1","key":"pmed.1004906.ref004","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.eururo.2018.08.036","article-title":"Epidemiology of renal cell carcinoma","volume":"75","author":"U Capitanio","year":"2019","journal-title":"Eur Urol"},{"issue":"10","key":"pmed.1004906.ref005","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/S0022-2275(20)38606-5","article-title":"Abnormal cholesterol metabolism in renal clear cell carcinoma","volume":"28","author":"RL Gebhard","year":"1987","journal-title":"J Lipid Res"},{"issue":"4","key":"pmed.1004906.ref006","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3109\/00313021003785746","article-title":"Differential diagnosis of renal tumours with clear cell histology","volume":"42","author":"VE Reuter","year":"2010","journal-title":"Pathology"},{"issue":"1","key":"pmed.1004906.ref007","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1152\/physrev.00033.2011","article-title":"Pathophysiology of human visceral obesity: an update","volume":"93","author":"A Tchernof","year":"2013","journal-title":"Physiol Rev"},{"issue":"11","key":"pmed.1004906.ref008","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41580-021-00390-6","article-title":"The aetiology and molecular landscape of insulin resistance","volume":"22","author":"DE James","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"pmed.1004906.ref009","article-title":"Adipose tissue in control of metabolism","volume":"231","author":"L Luo","year":"2016","journal-title":"J Endocrinol"},{"issue":"8","key":"pmed.1004906.ref010","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrc1408","article-title":"Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms","volume":"4","author":"EE Calle","year":"2004","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"pmed.1004906.ref011","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2019-000741","article-title":"Relationship of obesity to adipose tissue insulin resistance","volume":"8","author":"J Jiang","year":"2020","journal-title":"BMJ Open Diabetes Res Care"},{"issue":"3","key":"pmed.1004906.ref012","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s12079-019-00512-y","article-title":"Insulin and insulin-like growth factors act as renal cell cancer intratumoral regulators","volume":"13","author":"W Solarek","year":"2019","journal-title":"J Cell Commun Signal"},{"issue":"1","key":"pmed.1004906.ref013","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002724","article-title":"The influence of obesity-related factors in the etiology of renal cell carcinoma\u2014a mendelian randomization study","volume":"16","author":"M Johansson","year":"2019","journal-title":"PLoS Med"},{"issue":"2","key":"pmed.1004906.ref014","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/ijc.28352","article-title":"Hysterectomy and kidney cancer risk: a meta-analysis","volume":"134","author":"S Karami","year":"2014","journal-title":"Int J Cancer"},{"issue":"4","key":"pmed.1004906.ref015","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.euf.2017.01.006","article-title":"Variability of sex disparities in cancer incidence over 30 years: the striking case of kidney cancer","volume":"4","author":"G Scelo","year":"2018","journal-title":"Eur Urol Focus"},{"issue":"9","key":"pmed.1004906.ref016","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1158\/1055-9965.EPI-20-0246","article-title":"Association of sex hormones with risk of cancers of the pancreas, kidney, and brain in the UK Biobank Cohort Study","volume":"29","author":"R Peila","year":"2020","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"1","key":"pmed.1004906.ref017","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1038\/s41467-024-46927-z","article-title":"Phenome-wide Mendelian randomisation analysis of 378,142 cases reveals risk factors for eight common cancers","volume":"15","author":"M Went","year":"2024","journal-title":"Nat Commun"},{"issue":"6","key":"pmed.1004906.ref018","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1158\/1055-9965.EPI-19-1623","article-title":"Diabetes, glycated hemoglobin, and risk of cancer in the UK Biobank Study","volume":"29","author":"R Peila","year":"2020","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"11","key":"pmed.1004906.ref019","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1158\/1055-9965.EPI-23-0558","article-title":"Kidney function and risk of renal cell carcinoma","volume":"32","author":"K Alcala","year":"2023","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"18","key":"pmed.1004906.ref020","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1158\/0008-5472.CAN-20-1281","article-title":"Circulating insulin-like growth factor-I concentrations and risk of 30 cancers: prospective analyses in UK Biobank","volume":"80","author":"A Knuppel","year":"2020","journal-title":"Cancer Res"},{"issue":"8","key":"pmed.1004906.ref021","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrendo.2014.94","article-title":"Obesity and cancer--mechanisms underlying tumour progression and recurrence","volume":"10","author":"J Park","year":"2014","journal-title":"Nat Rev Endocrinol"},{"issue":"12","key":"pmed.1004906.ref022","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1200\/JCO.2010.31.5200","article-title":"Total cholesterol and cancer risk in a large prospective study in Korea","volume":"29","author":"CM Kitahara","year":"2011","journal-title":"J Clin Oncol"},{"issue":"11","key":"pmed.1004906.ref023","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/CIRCULATIONAHA.115.020406","article-title":"Shared risk factors in cardiovascular disease and cancer","volume":"133","author":"RJ Koene","year":"2016","journal-title":"Circulation"},{"issue":"12","key":"pmed.1004906.ref024","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41577-018-0066-7","article-title":"Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer","volume":"18","author":"SA Jones","year":"2018","journal-title":"Nat Rev Immunol"},{"issue":"6917","key":"pmed.1004906.ref025","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"LM Coussens","year":"2002","journal-title":"Nature"},{"issue":"3","key":"pmed.1004906.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"C Sudlow","year":"2015","journal-title":"PLoS Med"},{"key":"pmed.1004906.ref027","doi-asserted-by":"crossref","DOI":"10.3402\/gha.v3i0.4643","article-title":"The V\u00e4sterbotten Intervention Programme: background, design and implications","volume":"3","author":"M Norberg","year":"2010","journal-title":"Glob Health Action"},{"issue":"5","key":"pmed.1004906.ref028","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41588-024-01725-7","article-title":"Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions","volume":"56","author":"MP Purdue","year":"2024","journal-title":"Nat Genet"},{"issue":"1","key":"pmed.1004906.ref029","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a040501","article-title":"Mendelian randomization: concepts and scope","volume":"12","author":"RC Richmond","year":"2022","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"12","key":"pmed.1004906.ref030","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/aje\/kwq332","article-title":"Odds ratios for mediation analysis for a dichotomous outcome","volume":"172","author":"TJ Vanderweele","year":"2010","journal-title":"Am J Epidemiol"},{"issue":"7","key":"pmed.1004906.ref031","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"S Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"issue":"6","key":"pmed.1004906.ref032","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/ije\/dyx028","article-title":"Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique","volume":"45","author":"FP Hartwig","year":"2016","journal-title":"Int J Epidemiol"},{"issue":"2","key":"pmed.1004906.ref033","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/ije\/dyu176","article-title":"Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways","volume":"44","author":"S Burgess","year":"2015","journal-title":"Int J Epidemiol"},{"issue":"5","key":"pmed.1004906.ref034","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10654-021-00757-1","article-title":"Mendelian randomisation for mediation analysis: current methods and challenges for implementation","volume":"36","author":"AR Carter","year":"2021","journal-title":"Eur J Epidemiol"},{"issue":"1","key":"pmed.1004906.ref035","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/ije\/dyr233","article-title":"Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease","volume":"41","author":"CL Relton","year":"2012","journal-title":"Int J Epidemiol"},{"key":"pmed.1004906.ref036","doi-asserted-by":"crossref","first-page":"290","DOI":"10.2307\/270723","article-title":"Asymptotic confidence intervals for indirect effects in structural equation models","volume":"13","author":"ME Sobel","year":"1982","journal-title":"Sociol Methodol"},{"issue":"1","key":"pmed.1004906.ref037","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s42003-022-03272-5","article-title":"Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization","volume":"5","author":"M Vabistsevits","year":"2022","journal-title":"Commun Biol"},{"issue":"1","key":"pmed.1004906.ref038","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12933-018-0762-4","article-title":"Association between insulin resistance and the development of cardiovascular disease","volume":"17","author":"V Ormazabal","year":"2018","journal-title":"Cardiovasc Diabetol"},{"issue":"5","key":"pmed.1004906.ref039","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.bbalip.2011.10.003","article-title":"Hypertriglyceridemia secondary to obesity and diabetes","volume":"1821","author":"S Subramanian","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"pmed.1004906.ref040","article-title":"Synthesis and regulation of sex hormone-binding globulin in obesity","author":"A Hautanen","year":"2000","journal-title":"Int J Obes Relat Metab Disord"},{"issue":"6","key":"pmed.1004906.ref041","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1161\/CIRCRESAHA.116.305697","article-title":"Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms","volume":"116","author":"JE Hall","year":"2015","journal-title":"Circ Res"},{"issue":"4","key":"pmed.1004906.ref042","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1210\/jcem-71-4-929","article-title":"Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity","volume":"71","author":"B Zumoff","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"pmed.1004906.ref043","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1210\/jc.2004-0372","article-title":"Obesity, metabolic syndrome, and cardiovascular disease","volume":"89","author":"SM Grundy","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"pmed.1004906.ref044","first-page":"1317","article-title":"The relationship between blood pressure and risk of renal cell carcinoma","volume":"51","author":"K Alcala","year":"2022","journal-title":"Int J Epidemiol"},{"issue":"12","key":"pmed.1004906.ref045","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1158\/2159-8290.CD-21-0211","article-title":"Cholesterol auxotrophy as a targetable vulnerability in clear cell renal cell carcinoma","volume":"11","author":"R Riscal","year":"2021","journal-title":"Cancer Discov"},{"issue":"1","key":"pmed.1004906.ref046","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/ije\/dyz053","article-title":"The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers","volume":"49","author":"J Fritz","year":"2020","journal-title":"Int J Epidemiol"},{"issue":"7047","key":"pmed.1004906.ref047","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1136\/bmj.312.7047.1659","article-title":"Inflation in epidemiology: \u201cthe proof and measurement of association between two things\u201d revisited","volume":"312","author":"GD Smith","year":"1996","journal-title":"BMJ"},{"issue":"5","key":"pmed.1004906.ref048","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1093\/ije\/dyad082","article-title":"Exploring regression dilution bias using repeat measurements of 2858 variables in \u226449\u200a000 UK Biobank participants","volume":"52","author":"CE Rutter","year":"2023","journal-title":"Int J Epidemiol"},{"issue":"3","key":"pmed.1004906.ref049","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/cen.12086","article-title":"Sex hormone binding globulin and insulin resistance","volume":"78","author":"IR Wallace","year":"2013","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"2","key":"pmed.1004906.ref050","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2337\/db11-0727","article-title":"Potential role of tumor necrosis factor-\u03b1 in downregulating sex hormone-binding globulin","volume":"61","author":"R Sim\u00f3","year":"2012","journal-title":"Diabetes"},{"issue":"12","key":"pmed.1004906.ref051","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.2337\/db10-0179","article-title":"Relationships of circulating sex hormone-binding globulin with metabolic traits in humans","volume":"59","author":"A Peter","year":"2010","journal-title":"Diabetes"},{"issue":"1","key":"pmed.1004906.ref052","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1210\/er.2010-0013","article-title":"The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders","volume":"32","author":"WL Miller","year":"2011","journal-title":"Endocr Rev"},{"issue":"9","key":"pmed.1004906.ref053","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/aje\/kwx246","article-title":"Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population","volume":"186","author":"A Fry","year":"2017","journal-title":"Am J Epidemiol"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1004906","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:11:11Z","timestamp":1778159471000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004906"}},"subtitle":[],"editor":[{"given":"Steven C","family":"Moore","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004906","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]}}}