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dc.contributor.authorZheng, Jie
dc.contributor.authorZhang, Yuemiao
dc.contributor.authorRasheed, Humaira
dc.contributor.authorWalker, Venexia
dc.contributor.authorSugawara, Yuka
dc.contributor.authorLi, Jiachen
dc.contributor.authorLeng, Yue
dc.contributor.authorElsworth, Benjamin
dc.contributor.authorWootton, Robyn E
dc.contributor.authorFang, Si
dc.contributor.authorYang, Qian
dc.contributor.authorBurgess, Stephen
dc.contributor.authorHaycock, Philip C
dc.contributor.authorBorges, Maria Carolina
dc.contributor.authorCho, Yoonsu
dc.contributor.authorCarnegie, Rebecca
dc.contributor.authorHowell, Amy
dc.contributor.authorRobinson, Jamie
dc.contributor.authorThomas, Laurent F
dc.contributor.authorBrumpton, Ben Michael
dc.contributor.authorHveem, Kristian
dc.contributor.authorHallan, Stein
dc.contributor.authorFranceschini, Nora
dc.contributor.authorMorris, Andrew P
dc.contributor.authorKöttgen, Anna
dc.contributor.authorPattaro, Cristian
dc.contributor.authorWuttke, Matthias
dc.contributor.authorYamamoto, Masayuki
dc.contributor.authorKashihara, Naoki
dc.contributor.authorAkiyama, Masato
dc.contributor.authorKanai, Masahiro
dc.contributor.authorMatsuda, Koichi
dc.contributor.authorKamatani, Yoichiro
dc.contributor.authorOkada, Yukinori
dc.contributor.authorWalters, Robin
dc.contributor.authorMillwood, Iona Y
dc.contributor.authorChen, Zhengming
dc.contributor.authorDavey Smith, George
dc.contributor.authorBarbour, Sean
dc.contributor.authorYu, Canqing
dc.contributor.authorÅsvold, Bjørn Olav
dc.contributor.authorZhang, Hong
dc.contributor.authorGaunt, Tom R
dc.date.accessioned2021-10-25T23:31:19Z
dc.date.available2021-10-25T23:31:19Z
dc.date.issued2021-10-20
dc.identifier.issn0300-5771
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329881
dc.description.abstractBACKGROUND: 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. METHODS: 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 <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included. RESULTS: 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 >25 kg/m2. CONCLUSIONS: 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.
dc.description.sponsorshipThis research has been conducted using the UK Biobank resource under Application Numbers ‘40135’ and ‘15825’. J.Z. is funded by a Vice-Chancellor Fellowship from the University of Bristol. This research was also funded by the UK Medical Research Council Integrative Epidemiology Unit [MC_UU_00011/1, MC_UU_00011/4 and MC_UU_00011/7]. J.Z. is supported by the Academy of Medical Sciences (AMS) Springboard Award, the Wellcome Trust, the Government Department of Business, Energy and Industrial Strategy (BEIS), the British Heart Foundation and Diabetes UK [SBF006\1117]. This study was funded/supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (G.D.S., T.R.G. and R.E.W.). This study received funding from the UK Medical Research Council [MR/R013942/1]. J.Z., Y.M.Z. and T.R.G are funded by a BBSRC Innovation fellowship. J.Z. is supported by the Shanghai Thousand Talents Program. Y.M.Z. is supported by the National Natural Science Foundation of China [81800636]. H.Z. is supported by the Training Program of the Major Research Plan of the National Natural Science Foundation of China [91642120], a grant from the Science and Technology Project of Beijing, China [D18110700010000] and the University of Michigan Health System–Peking University Health Science Center Joint Institute for Translational and Clinical Research [BMU2017JI007]. N.F. is supported by the National Institutes of Health awards R01-MD012765, R01-DK117445 and R21-HL140385. R.C. is funded by a Wellcome Trust GW4 Clinical Academic Training Fellowship [WT 212557/Z/18/Z]. The Trøndelag Health Study (the HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority and the Norwegian Institute of Public Health. M.C.B. is supported by the UK Medical Research Council (MRC) Skills Development Fellowship [MR/P014054/1]. S.F. is supported by a Wellcome Trust PhD studentship [WT108902/Z/15/Z]. Q.Y. is funded by a China Scholarship Council PhD scholarship [CSC201808060273]. Y.C. was supported by the National Key R&D Program of China [2016YFC0900500, 2016YFC0900501 and 2016YFC0900504]. The China Kadoorie Biobank baseline survey and the first resurvey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust [202922/Z/16/Z, 088158/Z/09/Z and 104085/Z/14/Z]. Japan-Kidney-Biobank was supported by AMED under Grant Number 20km0405210. P.C.H. is supported by Cancer Research UK [grant number: C18281/A19169]. A.K. was supported by DFG KO 3598/5–1. N.F. is supported by NIH awards R01-DK117445, R01-MD012765 and R21-HL140385. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleTrans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease.
dc.typeArticle
prism.publicationDate2021
prism.publicationNameInt J Epidemiol
dc.identifier.doi10.17863/CAM.77326
dcterms.dateAccepted2021-09-01
rioxxterms.versionofrecord10.1093/ije/dyab203
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-10-20
dc.contributor.orcidZheng, Jie [0000-0002-6623-6839]
dc.contributor.orcidWalker, Venexia [0000-0001-5064-446X]
dc.contributor.orcidElsworth, Benjamin [0000-0001-7328-4233]
dc.contributor.orcidWootton, Robyn E [0000-0003-3961-3202]
dc.contributor.orcidYang, Qian [0000-0001-8778-4132]
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.contributor.orcidDavey Smith, George [0000-0002-1407-8314]
dc.identifier.eissn1464-3685
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/R013942/1)
cam.issuedOnline2021-10-20


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International