Evidence map›Paper›PMID 34999880›Full record

ArticleInternational journal of epidemiology2022

Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease.

Jie Zheng, Yuemiao Zhang, Humaira Rasheed, Venexia Walker, Yuka Sugawara, Jiachen Li, Yue Leng, Benjamin Elsworth, Robyn E Wootton, Si Fang and 33 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of epidemiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 4 pooled it
11.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 4 syntheses or guidelines pooled it, 114 citations in OpenAlex.

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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors at 20 institutions in 8 countries.

Jie ZhengMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.ORCID 0000-0002-6623-6839
Yuemiao ZhangRenal 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.
Humaira RasheedMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Venexia WalkerMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.ORCID 0000-0001-5064-446X
Yuka SugawaraDivision of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan.
Jiachen LiDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. R. China.
Yue LengDepartment of Psychiatry, University of California, San Francisco, CA, USA.
Benjamin ElsworthMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.ORCID 0000-0001-7328-4233
Robyn E WoottonMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.ORCID 0000-0003-3961-3202
Si FangMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Qian YangMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.ORCID 0000-0001-8778-4132
Stephen BurgessMRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK.
Philip C HaycockMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Maria Carolina BorgesMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Yoonsu ChoMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Rebecca CarnegieMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Amy HowellMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Jamie RobinsonMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Laurent F ThomasK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Ben Michael BrumptonMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Stein HallanDepartment of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Nora FranceschiniDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Andrew P MorrisDivision of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK.
Anna KöttgenInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Cristian PattaroEurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
Matthias WuttkeInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Masayuki YamamotoTohoku Medical Megabank Organization and Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.
Naoki KashiharaDepartment of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Masato AkiyamaLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Masahiro KanaiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Koichi MatsudaDepartment of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, the University of Tokyo, Tokyo, Japan.
Yoichiro KamataniLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Yukinori OkadaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Robin WaltersClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Iona Y MillwoodClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Zhengming ChenClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
George Davey SmithMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.ORCID 0000-0002-1407-8314
Sean BarbourDivision of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada.
Canqing YuDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. R. China.
Bjørn Olav ÅsvoldK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Hong ZhangRenal 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.
Tom R GauntMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
University of Bristol · GBNorwegian University of Science and Technology · NOPeking University · CNUniversity of Oxford · GBUniversity Hospitals Bristol NHS Foundation Trust · GBUniversity of Freiburg · DEEurac Research · ITHarvard University · USKawasaki Medical School · JPKyushu University · JPRIKEN Center for Integrative Medical Sciences · JPThe University of Osaka · JPThe University of Tokyo · JPTohoku University · JPUniversity of British Columbia · CAUniversity of California, San Francisco · USUniversity of Cambridge · GBUniversity of Manchester · GBUniversity of North Carolina at Chapel Hill · USUniversity of Tokyo Hospital · JP

Funding

Leveraging ancestry to map kidney lociR01MD012765 · NIMHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRANCESCHINI, NORA · 2017 to 2021
$3.6M
Genetics of kidney disease in diverse populationsR01DK117445 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRANCESCHINI, NORA · 2018 to 2022
$2.7M
British Heart Foundation CH/12/2/29428British Heart Foundation RG/13/13/30194British Heart Foundation RG/18/13/33946Cancer Research UK 16896Cancer Research UK 29186Medical Research Council MC_PC_13049Medical Research Council MC_PC_14135Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_U137686851Medical Research Council MC_UU_00002/7Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/4Medical Research Council MC_UU_00011/7Medical Research Council MC_UU_00017/1Medical Research Council MC_UU_12026/2Medical Research Council MR/R013942/1NIDDK NIH HHS R01 DK117445NIMHD NIH HHS R01 MD012765Wellcome Trust 204623/Z/16/ZWellcome Trust 212946/Z/18/Z
6 · The paper itself

Abstract

backgroundThis 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.

methodsA 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.

resultsEight 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.

conclusionsEight 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.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Renal Insufficiency, ChronicGenome-Wide Association StudyHumansMendelian Randomization AnalysisRandom Allocationcardiometabolic risk factorscausalitychronic kidney diseaseMendelian randomizationtrans-ethnic study

Identifiers

PMID34999880
PMCPMC8743120
OpenAlexW3083581581

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.