{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T21:38:45Z","timestamp":1793137125496,"version":"4.5.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK Biobank resource under Application","award":["40135"],"award-info":[{"award-number":["40135"]}]},{"name":"UK Biobank resource under Application","award":["15825"],"award-info":[{"award-number":["15825"]}]},{"name":"Vice-Chancellor Fellowship from the University of Bristol"},{"name":"UK Medical Research Council Integrative Epidemiology Unit","award":["MC_UU_00011\/1"],"award-info":[{"award-number":["MC_UU_00011\/1"]}]},{"name":"UK Medical Research Council Integrative Epidemiology Unit","award":["MC_UU_00011\/4"],"award-info":[{"award-number":["MC_UU_00011\/4"]}]},{"name":"UK Medical Research Council Integrative Epidemiology Unit","award":["MC_UU_00011\/7"],"award-info":[{"award-number":["MC_UU_00011\/7"]}]},{"name":"Academy of Medical Sciences (AMS) Springboard Award"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government Department of Business"},{"name":"Energy and Industrial Strategy"},{"name":"British Heart Foundation and Diabetes UK","award":["SBF006\\1117"],"award-info":[{"award-number":["SBF006\\1117"]}]},{"name":"NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol"},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R013942\/1"],"award-info":[{"award-number":["MR\/R013942\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BBSRC Innovation fellowship"},{"name":"Shanghai Thousand Talents Program"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800636"],"award-info":[{"award-number":["81800636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Training Program of the Major Research Plan of the National Natural Science Foundation of China","award":["91642120"],"award-info":[{"award-number":["91642120"]}]},{"name":"Science and Technology Project of Beijing, China","award":["D18110700010000"],"award-info":[{"award-number":["D18110700010000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of &amp;lt;60\u2009ml\/min\/1.73\u00a0m2. Ultimately, 51\u00a0672 CKD cases and 958\u00a0102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13\u00a0093 CKD cases and 238\u00a0118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank\/ToMMo were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of &amp;gt;25\u2009kg\/m2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ije\/dyab203","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T07:26:03Z","timestamp":1631085963000},"page":"1995-2010","source":"Crossref","is-referenced-by-count":115,"title":["Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-6839","authenticated-orcid":false,"given":"Jie","family":"Zheng","sequence":"first","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Rasheed","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"},{"name":"K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5064-446X","authenticated-orcid":false,"given":"Venexia","family":"Walker","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"},{"name":"Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-4233","authenticated-orcid":false,"given":"Benjamin","family":"Elsworth","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3961-3202","authenticated-orcid":false,"given":"Robyn E","family":"Wootton","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Fang","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-4132","authenticated-orcid":false,"given":"Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK"},{"name":"Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C","family":"Haycock","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carolina","family":"Borges","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonsu","family":"Cho","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Carnegie","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Howell","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Robinson","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent F","family":"Thomas","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway"},{"name":"Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben Michael","family":"Brumpton","sequence":"additional","affiliation":[{"name":"MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK"},{"name":"K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway"},{"name":"Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Hveem","sequence":"additional","affiliation":[{"name":"K.G. 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