{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:25:33Z","timestamp":1777292733051,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council Integrative Epidemiology Unit"},{"DOI":"10.13039\/501100000883","name":"University of Bristol","doi-asserted-by":"publisher","award":["MC_UU_00011\/5"],"award-info":[{"award-number":["MC_UU_00011\/5"]}],"id":[{"id":"10.13039\/501100000883","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000269","name":"Economic and Social Research Council","doi-asserted-by":"publisher","award":["ES\/N000498\/1"],"award-info":[{"award-number":["ES\/N000498\/1"]}],"id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Bristol Vice-Chancellor\u2019s Fellowship"},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18281\/A19169"],"award-info":[{"award-number":["C18281\/A19169"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background: Sex hormone-binding globulin (SHBG) is a circulating glycoprotein and a regulator of sex hormone levels, which has been shown to influence various traits and diseases. The molecular nature of SHBG makes it a feasible target for preventative or therapeutic interventions. A systematic study of its effects across the human phenome may uncover novel associations. Methods: We used a Mendelian randomization phenome-wide association study (MR-pheWAS) approach to systematically appraise the potential functions of SHBG while reducing potential biases such as confounding and reverse causation common to the literature. We searched for potential causal effects of SHBG in UK Biobank (N\u2009=\u2009334\u2009977) and followed-up our top findings using two-sample MR analyses to evaluate whether estimates may be biased due to horizontal pleiotropy. Results: Results of the MR-pheWAS across over 21\u2009000 outcome phenotypes identified 12 phenotypes associated with genetically elevated SHBG after Bonferroni correction for multiple testing. Follow-up analysis using two-sample MR indicated the associations of increased natural log SHBG with higher impedance of the arms and whole body, lower pulse rate, lower bone density, higher odds of hip replacement, lower odds of high cholesterol or cholesterol medication use and higher odds of gallbladder removal. Conclusions: Our systematic MR-pheWAS of SHBG, which was comprehensive to the range of phenotypes available in UK Biobank, suggested that higher circulating SHBG affects the body impedance, bone density and cholesterol levels, among others. These phenotypes should be prioritized in future studies aiming to investigate the biological effects of SHBG or develop targets for therapeutic intervention.<\/jats:p>","DOI":"10.1093\/hmg\/ddz269","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T12:07:44Z","timestamp":1578312464000},"page":"1824-1832","source":"Crossref","is-referenced-by-count":20,"title":["Impact of sex hormone-binding globulin on the human phenome"],"prefix":"10.1093","volume":"29","author":[{"given":"Ryan","family":"Arathimos","sequence":"first","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK"},{"name":"Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London, UK"},{"name":"NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise A C","family":"Millard","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK"},{"name":"Intelligent Systems Laboratory, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua A","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline L","family":"Relton","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Suderman","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"},{"name":"Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"issue":"1","key":"2020072105164096500_ref1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1365-2265.1974.tb03298.x","article-title":"Sex-hormone-binding globulin","volume":"3","author":"Anderson","year":"1974","journal-title":"Clin. 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