title: Genetic correlations of brain lesion distribution in multiple sclerosis: an exploratory study.
abstract: OBJECTIVE
  In MS, the total brain lesion volume and spatial distribution of lesions across the brain vary widely among individual patients. We hypothesized that spatial distribution may be partially driven by genetic predisposition, and we aimed to explore relations among candidate genes and the spatial distribution of white matter brain lesions in MS.
  
  
  METHODS
  Genotypes of 69 SNPs in 208 patients with MS were related to the spatial distribution of T2 brain lesions. Lesions were manually outlined on MR images, and binary lesion masks were produced and registered to a common space. With Randomise software, the lesion masks were related to genotype by using a voxelwise nonparametric GLM approach, followed by clusterwise analysis. We used a DNA chip with SNPs selected from the literature on MS susceptibility, severity, and phenotypes.
  
  
  RESULTS
  For 11 of these SNPs, 1 of the genotypes expressed significant clusters of increased or decreased lesion probability in varying, predominantly periventricular, brain regions. When we statistically controlled the voxelwise analyses for effects of total brain lesion volume, only 1 SNP remained significant: rs2227139, located within the MHC class II region. This SNP retained its periventricular cluster of significantly increased lesion probability for the heterozygote genotype.
  
  
  CONCLUSIONS
  Heterozygosity of rs2227139 (MHC class II region) is associated with increased right frontal periventricular lesion probability (P<.01). Ten other SNPs showed associations between genotype and spatial lesion distribution that are partly explained by total lesion volume.
authors: VU University Medical Center, Department of Neurology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. m.sombekke@vumc.nl
authors: M H
authors: MH
authors: Sombekke
authors: M M
authors: MM
authors: Vellinga
authors: B M J
authors: BM
authors: Uitdehaag
authors: F
authors: F
authors: Barkhof
authors: C H
authors: CH
authors: Polman
authors: D
authors: D
authors: Arteta
authors: D
authors: D
authors: Tejedor
authors: A
authors: A
authors: Martinez
authors: J B A
authors: JB
authors: Crusius
authors: A S
authors: AS
authors: Peña
authors: J J G
authors: JJ
authors: Geurts
authors: H
authors: H
authors: Vrenken
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D020869:Gene Expression Profiling; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D000949:Histocompatibility Antigens Class II