title: Genetic susceptibility to multiple sclerosis: Brain structure and cognitive function in the general population.
abstract: BACKGROUND
  Multiple sclerosis (MS) affects brain structure and cognitive function and has a heritable component. Over a 100 common genetic risk variants have been identified, but most carriers do not develop MS. For other neurodegenerative diseases, risk variants have effects outside patient populations, but this remains uninvestigated for MS.
  
  
  OBJECTIVE
  To study the effect of MS-associated genetic variants on brain structure and cognitive function in the general population.
  
  
  METHODS
  We studied middle-aged and elderly individuals (mean age = 65.7 years) from the population-based Rotterdam Study. We determined 107 MS variants and additionally created a risk score combining all variants. Magnetic resonance imaging ( N = 4710) was performed to obtain measures of brain macrostructure, white matter microstructure, and gray matter voxel-based morphometry. A cognitive test battery ( N = 7556) was used to test a variety of cognitive domains.
  
  
  RESULTS
  The MS risk score was associated with smaller gray matter volume over the whole brain (βstandardized= -0.016; p = 0.044), but region-specific analyses did not survive multiple testing correction. Similarly, no significant associations with brain structure were observed for individual variants. For cognition, rs2283792 was significantly associated with poorer memory (β = -0.064; p = 3.4 × 10-5).
  
  
  CONCLUSIONS
  Increased genetic susceptibility to MS may affect brain structure and cognition in persons without disease, pointing to a "hidden burden" of MS.
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Radiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Neurology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Mohammad Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Radiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Department of Radiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Medical Informatics, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Gennady V
authors.initials: GV
authors.lastname: Roshchupkin
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Radiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Neurology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Department of Neurology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Rogier Q
authors.initials: RQ
authors.lastname: Hintzen
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands/Department of Radiology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Hieab Hh
authors.initials: HH
authors.lastname: Adams
mesh_terms: D000368:Aged; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology*; D009426:Netherlands
keywords: Epidemiology; genetics; magnetic resonance imaging; multiple sclerosis