title: Large differences in adiponectin levels have no clear effect on multiple sclerosis risk: A Mendelian randomization study.
abstract: BACKGROUND
  Mendelian randomization (MR) studies have demonstrated strong support for an association between genetically increased body mass index and risk of multiple sclerosis (MS). The adipokine adiponectin may be a potential mechanism linking body mass to risk of MS.
  
  
  OBJECTIVE
  To evaluate whether genetically increased adiponectin levels influence risk of MS.
  
  
  METHODS
  Using genome-wide significant single nucleotide polymorphisms (SNPs) for adiponectin, we undertook an MR study to estimate the effect of adiponectin on MS. This method prevents bias due to reverse causation and minimizes bias due to confounding. Sensitivity analyses were performed to evaluate the assumptions of MR.
  
  
  RESULTS
  MR analyses did not support a role for genetically elevated adiponectin in risk of MS (odds ratio (OR) = 0.93 per unit increase in natural-log-transformed adiponectin, equivalent to a two-standard deviation increase in adiponectin on the absolute scale; 95% confidence interval (CI) = 0.66-1.33; p = 0.61). Further MR analysis suggested that genetic variation at the adiponectin gene, which influences adiponectin level, does not impact MS risk. Sensitivity analyses, including MR-Egger regression, suggested no bias due to pleiotropy.
  
  
  CONCLUSIONS
  Lifelong genetically increased adiponectin levels in humans have no clear effect on risk of MS. Other biological factors driving the association between body mass and MS should be investigated.
authors.affiliation: Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Devorak
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Mokry
authors.affiliation: Department of Human Genetics, McGill University, Montréal, QC, Canada.
authors.forename: John A
authors.initials: JA
authors.lastname: Morris
authors.affiliation: Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Forgetta
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawcer
authors.affiliation: Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada/Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada/Department of Human Genetics, McGill University, Montréal, QC, Canada/Department of Medicine, McGill University, Montréal, QC, Canada/Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D006801:Humans; D057182:Mendelian Randomization Analysis / Q000379:methods*; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin
keywords: Mendelian randomization analysis; Multiple sclerosis; adiponectin; genetic epidemiology