Obesity and Multiple Sclerosis: A Mendelian Randomization Study

PLoS Medicine
Lauren E MokryJ Brent Richards


Observational studies have reported an association between obesity, as measured by elevated body mass index (BMI), in early adulthood and risk of multiple sclerosis (MS). However, bias potentially introduced by confounding and reverse causation may have influenced these findings. Therefore, we elected to perform Mendelian randomization (MR) analyses to evaluate whether genetically increased BMI is associated with an increased risk of MS. Employing a two-sample MR approach, we used summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the International MS Genetics Consortium (IMSGC), the largest genome-wide association studies for BMI and MS, respectively (GIANT: n = 322,105; IMSGC: n = 14,498 cases and 24,091 controls). Seventy single nucleotide polymorphisms (SNPs) were genome-wide significant (p < 5 x 10-8) for BMI in GIANT (n = 322,105) and were investigated for their association with MS risk in the IMSGC. The effect of each SNP on MS was weighted by its effect on BMI, and estimates were pooled to provide a summary measure for the effect of increased BMI upon risk of MS. Our results suggest that increased BMI influences MS susceptibility, where a 1 standard deviation increase in ge...Continue Reading


Sep 1, 1986·Controlled Clinical Trials·R DerSimonian, N Laird
Dec 1, 1996·Arteriosclerosis, Thrombosis, and Vascular Biology·S Lamon-FavaE J Schaefer
Oct 6, 1997·BMJ : British Medical Journal·M EggerC Minder
Jan 3, 2001·Pediatrics·M VisserTamara B Harris
Jan 10, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·F M van DielenJ W Greve
Apr 10, 2003·JAMA : the Journal of the American Medical Association·Katherine EspositoDario Giugliano
Apr 12, 2003·International Journal of Epidemiology·George Davey Smith, Shah Ebrahim
Sep 17, 2004·Biochemical and Biophysical Research Communications·Anna M WolfHerbert Tilg
Mar 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Giuseppe MatareseSerafino Zappacosta
Jul 13, 2006·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·M PugliattiI Milanov
Oct 21, 2006·Lancet Neurology·Sarah-Michelle OrtonCanadian Collaborative Study Group
May 12, 2007·International Journal of Clinical Practice·H E BaysSHIELD Investigators' Group
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
Apr 22, 2008·International Journal of Epidemiology·Nikolaos A PatsopoulosJohn P A Ioannidis
Jun 7, 2008·BMC Public Health·Anne BerghöferStefan N Willich
Oct 31, 2008·Lancet·Alastair Compston, Alasdair Coles
Nov 1, 2008·Bioinformatics·Andrew D JohnsonPaul I W de Bakker
Nov 11, 2009·Neurology·Kassandra L MungerAlberto Ascherio
Dec 3, 2009·Nature Reviews. Neurology·Alexandra DegenhardtGeorge C Ebers
Apr 20, 2010·Lancet Neurology·Nils Koch-Henriksen, Per Soelberg Sørensen
Aug 18, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·N J TimpsonGeorge Davey Smith
Oct 27, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J J Reilly, J Kelly
Nov 18, 2011·The New England Journal of Medicine·Markus JuonalaOlli T Raitakari
Dec 20, 2011·Circulation·Véronique L RogerAmerican Heart Association Statistics Committee and Stroke Statistics Subcommittee
Dec 23, 2011·Annals of Neurology·Nikolaos A PatsopoulosPaul I W de Bakker
Jan 19, 2012·JAMA : the Journal of the American Medical Association·Katherine M FlegalCynthia L Ogden
Feb 14, 2012·Multiple Sclerosis : Clinical and Laboratory Research·Anna Karin HedströmLars Alfredsson
Apr 4, 2013·Multiple Sclerosis : Clinical and Laboratory Research·Kassandra L MungerJennifer L Baker
Oct 1, 2013·Nature Genetics·International Multiple Sclerosis Genetics Consortium (IMSGC)Jacob L McCauley
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Feb 11, 2014·Handbook of Clinical Neurology·Douglas S Goodin
Feb 20, 2014·European Journal of Human Genetics : EJHG·Laura M HuckinsWTCCC3
Feb 27, 2014·JAMA : the Journal of the American Medical Association·Cynthia L OgdenKatherine M Flegal
Nov 8, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·W AhrensA Siani
Feb 13, 2015·Nature·Adam E LockeElizabeth K Speliotes
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Aug 26, 2015·PLoS Medicine·Lauren E MokryJ Brent Richards
Sep 15, 2015·Nature·UK10K ConsortiumNicole Soranzo


Oct 11, 2016·Mediators of Inflammation·José de Jesús Guerrero-GarcíaDaniel Ortuño-Sahagún
Dec 10, 2016·Nature Reviews. Neurology·Tomas OlssonLars Alfredsson
Mar 14, 2017·Multiple Sclerosis : Clinical and Laboratory Research·Marianna CorteseMultiple Sclerosis Conscript Service Database Study Group
Apr 12, 2017·International Journal of Epidemiology·Olena O Yavorska, Stephen Burgess
Jun 18, 2017·Nature Reviews. Neurology·Paolo A MuraroRiccardo Saccardi
Mar 12, 2018·Current Neurology and Neuroscience Reports·Marije J D Huitema, Geert J Schenk
Oct 12, 2017·Obesity Facts·Jakob KjellbergBetina Højgaard
Jan 30, 2018·Annals of the New York Academy of Sciences·Olga MatveevaMarkus Kleinewietfeld
Jan 9, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Adil Harroud, J Brent Richards
Oct 10, 2018·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Ruth Dobson, Gavin Giovannoni
Dec 6, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Samantha N FreedmanAshutosh K Mangalam
Feb 19, 2019·Current Environmental Health Reports·Maria Grau-PerezMaria Tellez-Plaza
Oct 19, 2017·Nature Immunology·Veronica De RosaGiuseppe Matarese
May 8, 2018·Cold Spring Harbor Perspectives in Medicine·Lars Alfredsson, Tomas Olsson
May 25, 2016·Scientific Reports·Amy E TaylorMarcus R Munafò
May 14, 2019·Multiple Sclerosis : Clinical and Laboratory Research·Jennifer GravesEmmanuelle Waubant
May 23, 2019·Neurodegenerative Disease Management·Dejan JakimovskiRobert Zivadinov
Jun 5, 2019·Continuum : Lifelong Learning in Neurology·Bardia Nourbakhsh, Ellen Mowry
Oct 13, 2019·World Journal of Surgery·Jamie R RobinsonJoshua C Denny
Mar 2, 2018·Evolution, Medicine, and Public Health·Riley M Bove
Oct 8, 2019·The International Journal of Neuroscience·Tobore Onojighofia Tobore
Feb 8, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Martin BiströmPeter Sundström
Jan 25, 2020·Annals of Neurology·Ruth DobsonGavin Giovannoni
Jan 16, 2020·Neurology. Neuroimmunology and Neuroinflammation·Benjamin M JacobsRuth Dobson
Mar 31, 2017·Neurology·Milena A GianfrancescoNetwork of Pediatric Multiple Sclerosis Centers
Nov 23, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Mahantesh I BiradarWen-Harn Pan
Apr 6, 2017·Frontiers in Immunology·Katrina J BingerMarkus Kleinewietfeld
Aug 9, 2019·Annals of Clinical and Translational Neurology·Emmanuelle WaubantAnnette Langer-Gould
Oct 31, 2019·Multiple Sclerosis Journal - Experimental, Translational and Clinical·S Blumenfeld KanA Miller
Apr 7, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Lazaros BelbasisIoanna Tzoulaki
Jun 13, 2020·Journal of Neurology·Marijne Vandebergh, An Goris
Aug 24, 2017·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Gene S Fisch
Jan 9, 2019·Frontiers in Neuroscience·Peter Van Dyken, Baptiste Lacoste
Mar 11, 2020·Frontiers in Immunology·Rebeca Arroyo HorneroMarkus Kleinewietfeld
Jun 13, 2020·Immunometabolism·Colleen E Hayes, James M Ntambi
Apr 21, 2017·Frontiers in Neurology·Elizabeth A MillsYang Mao-Draayer
Jun 6, 2018·Frontiers in Neurology·Ali ManouchehriniaRyan Ramanujam
Jul 24, 2019·Frontiers in Endocrinology·Paola de CandiaGiuseppe Matarese
May 31, 2019·Neurological Research·Efthimios DardiotisGeorgios M Hadjigeorgiou
Jul 31, 2020·Journal of Neurology·Shuai YuanSusanna C Larsson
Jun 6, 2018·International Journal of Molecular Sciences·Véronique Ferret-SenaArmando Sena
Aug 9, 2020·Journal of Molecular Neuroscience : MN·Tobore Onojighofia Tobore
Oct 24, 2018·Annals of Clinical and Translational Neurology·Bardia NourbakhshEmmanuelle Waubant
Dec 11, 2020·Nutritional Neuroscience·Nicola VeroneseLuigi Fontana
Jan 8, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Hui LuGuo-Xiang Huang

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