Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes: Mendelian randomization study

Susanna C LarssonMETASTROKE Collaboration and NINDS Stroke Genetics Network (SiGN)


To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes. MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (conventional) and weighted median approaches, and MR-Egger regression was used to explore pleiotropy. The number of single nucleotide polymorphisms (SNPs) used as instrumental variables was 49 for T2D, 36 for fasting glucose, 18 for fasting insulin, and 77 for BMI. Genome-wide association study data of SNP-stroke associations were derived from METASTROKE and the Stroke Genetics Network (n = 18,476 ischemic stroke cases and 37,296 controls). Conventional MR analysis showed associations between genetically predicted T2D and large artery stroke (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.16-1.40, p = 3.3 × 10-7) and small vessel stroke (OR 1.21, 95% CI 1.10-1.33, p = 8.9 × 10-5) but not cardioembolic stroke (OR 1.06, 95% CI 0.97-1.15, p = 0.17). The association of T2D with large artery stroke but not small vessel stroke was consistent in a sensitivity ana...Continue Reading


Mar 20, 2018·Cardiovascular Research·Rainer Malik, Martin Dichgans
Nov 6, 2017·Current Diabetes Reports·Jordi MerinoJames B Meigs
Apr 25, 2018·Stroke; a Journal of Cerebral Circulation·Junfeng LiuMatthew Traylor
Feb 21, 2019·Annals of Neurology·Susanna C LarssonHugh S Markus
Aug 23, 2019·Journal of Neurology·Huan CaiJialin Liang
Jan 25, 2020·Annals of Neurology·Sandro MariniInternational Stroke Genetics Consortium
Nov 13, 2019·The Journal of Clinical Endocrinology and Metabolism·Mark O GoodarziJerome I Rotter
May 22, 2020·Circulation Research·Mark O Goodarzi, Jerome I Rotter
Nov 12, 2019·Journal of Neurology·Petrea FridStroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), and the MRI-Genetics Interface Explorat
Sep 16, 2020·Nature Communications·Pascal M MutiePaul W Franks
Jun 26, 2018·Current Diabetes Reports·Rona J Strawbridge, Natalie R van Zuydam
Dec 18, 2019·Korean Circulation Journal·Wes SpillerSun Ha Jee
Jul 17, 2020·Frontiers in Cell and Developmental Biology·Xiaoying LiLitao Sun
Mar 17, 2020·Journal of Neurology·Huan CaiHao Zhang


Apr 12, 2003·International Journal of Epidemiology·George Davey Smith, Shah Ebrahim
Jan 30, 2007·Diabetic Medicine : a Journal of the British Diabetic Association·Nita G ForouhiNicholas J Wareham
Sep 11, 2007·Neuroimaging Clinics of North America·Colin P Derdeyn
Jun 10, 2008·The New England Journal of Medicine·Anushka PatelFlorence Travert
Jun 10, 2008·The New England Journal of Medicine·Hertzel C GersteinWilliam T Friedewald
Dec 18, 2009·Nature·Augustine KongKari Stefansson
Apr 27, 2010·Nature Genetics·Tobacco and Genetics Consortium
Jun 4, 2010·The American Journal of Clinical Nutrition·Emanuella De Lucia RolfeKen K Ong
Jun 29, 2010·Nature Genetics·Benjamin F VoightGIANT Consortium
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Feb 3, 2011·European Heart Journal·Matthias EndresAntoine M Hakim
Aug 14, 2012·Nature Genetics·Andrew P MorrisDIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
Sep 12, 2013·Stroke; a Journal of Cerebral Circulation·James F MeschiaNINDS SiGN Study
Oct 8, 2013·Nature Genetics·Cristen J WillerGlobal Lipids Genetics Consortium
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Jan 28, 2014·American Journal of Human Genetics·Michael V HolmesBrendan J Keating
Feb 1, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Mariana SelwanessJolanda J Wentzel
Oct 29, 2014·Nature Reviews. Neurology·Hugh S Markus, Steve Bevan
Dec 4, 2014·The Lancet. Diabetes & Endocrinology·Anoop Dinesh ShahHarry Hemingway
Feb 13, 2015·Nature·Adam E LockeElizabeth K Speliotes
May 29, 2015·International Journal of Epidemiology·Sara HäggEuropean Network for Genetic and Genomic Epidemiology Consortium
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Aug 19, 2015·Statistical Methods in Medical Research·Stephen BurgessSimon G Thompson
Nov 7, 2015·Journal of the American College of Cardiology·Thomas T van SlotenCoen D A Stehouwer
Dec 29, 2015·Lancet Neurology·NINDS Stroke Genetics Network (SiGN), International Stroke Genetics Consortium (ISGC)
Feb 18, 2016·The New England Journal of Medicine·Walter N KernanIRIS Trial Investigators
Mar 5, 2016·Neurology·Rainer MalikNINDS Stroke Genetics Network (SiGN)
Sep 9, 2016·Neurology·Mary E KrollMillion Women Study Collaborators

Related Concepts

Ischemic Cerebrovascular Accident
Genome-Wide Association Study
Diabetes Mellitus, Non-Insulin-Dependent
Biological Neural Networks
Mendelian Randomization Analysis
Magnetic Resonance Imaging
Genetic Pleiotropy
Structure of Large Artery
Odds Ratio

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