Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study.

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cam.issuedOnline2021-10-19
dc.contributor.authorLiu, Bowen
dc.contributor.authorMason, Amy M
dc.contributor.authorSun, Luanluan
dc.contributor.authorDi Angelantonio, Emanuele
dc.contributor.authorGill, Dipender
dc.contributor.authorBurgess, Stephen
dc.contributor.orcidGill, Dipender [0000-0001-7312-7078]
dc.date.accessioned2021-10-21T23:30:20Z
dc.date.available2021-10-21T23:30:20Z
dc.date.issued2021-10-19
dc.description.abstract(1) Aim: To investigate the causal effects of T2DM liability and glycated haemoglobin (HbA1c) levels on various cardiovascular disease outcomes, both in the general population and in non-diabetic individuals specifically. (2) Methods: We selected 243 variants as genetic instruments for T2DM liability and 536 variants for HbA1c. Linear Mendelian randomization analyses were performed to estimate the associations of genetically-predicted T2DM liability and HbA1c with 12 cardiovascular disease outcomes in 367,703 unrelated UK Biobank participants of European ancestries. We performed secondary analyses in participants without diabetes (HbA1c < 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c < 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p < 0.004, 0.05/12) with peripheral vascular disease, aortic valve stenosis, coronary artery disease, heart failure, ischaemic stroke, and any stroke. Genetically-predicted HbA1c was positively associated with coronary artery disease and any stroke. Mendelian randomization estimates generally shifted towards the null when excluding diabetic and pre-diabetic participants from analyses. (4) Conclusions: This genetic evidence supports causal effects of T2DM liability and HbA1c on a range of cardiovascular diseases, suggesting that improving glycaemic control could reduce cardiovascular risk in a general population, with greatest benefit in individuals with diabetes.
dc.description.sponsorshipStephen Burgess is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z). Dipender Gill is supported by the British Heart Foundation Centre of Research Excellence (RE/18/4/34215) at Imperial College London and a National Institute for Health Research Clinical Lectureship at St. George’s, University of London (CL-2020-16-001).
dc.identifier.doi10.17863/CAM.77178
dc.identifier.eissn2073-4425
dc.identifier.issn2073-4425
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329731
dc.languageeng
dc.publisherMDPI AG
dc.publisher.urlhttp://dx.doi.org/10.3390/genes12101644
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectaverage blood glucose
dc.subjectcardiovascular diseases
dc.subjecthemoglobin A1c
dc.subjectmendelian randomization
dc.subjecttype 2 diabetes mellitus
dc.subjectAortic Valve Stenosis
dc.subjectCardiovascular Diseases
dc.subjectCoronary Artery Disease
dc.subjectDiabetes Mellitus, Type 2
dc.subjectFemale
dc.subjectGenetic Association Studies
dc.subjectGenetic Predisposition to Disease
dc.subjectGenetic Variation
dc.subjectGlycated Hemoglobin
dc.subjectHeart Failure
dc.subjectHumans
dc.subjectIschemic Stroke
dc.subjectMale
dc.subjectMendelian Randomization Analysis
dc.subjectMiddle Aged
dc.subjectPeripheral Vascular Diseases
dc.subjectStroke
dc.titleGenetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study.
dc.typeArticle
dcterms.dateAccepted2021-10-17
prism.issueIdentifier10
prism.publicationDate2021
prism.publicationNameGenes (Basel)
prism.volume12
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
pubs.funder-project-idEuropean Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (CH/12/2/29428)
pubs.funder-project-idBritish Heart Foundation (RG/18/13/33946)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)
rioxxterms.licenseref.startdate2021-10-19
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/genes12101644
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