title: HLA-DRB1 and month of birth in multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) displays a month-of-birth effect, with an excess of individuals being born in the spring and a deficit in the winter. This effect was shown to be more pronounced in familial cases of MS. In the present study, we investigated whether this month-of-birth association has any relation to the principal MS susceptibility gene, HLA-DRB1.
  
  
  METHODS
  A total of 4,834 patients with MS, 4,056 controls, and 659 unaffected siblings from Canada, Sweden, and Norway were genotyped for the HLA-DRB1 gene. Month of birth was compared for patients, controls, and unaffected siblings with and without the MS risk allele HLA-DRB1*15.
  
  
  RESULTS
  Significantly fewer patients with MS carrying the HLA-DRB1*15 risk allele were born in November compared with patients not carrying this allele (p = 0.02). Additionally, patients with MS carrying HLA-DRB1*15 had a higher number of April births compared with patients with MS not carrying HLA-DRB1*15 (p = 0.004). These differences were not present in controls or unaffected siblings.
  
  
  CONCLUSIONS
  Month of birth, HLA-DRB1 genotype, and risk of multiple sclerosis are associated. The interaction of a seasonal risk factor with loci at or near HLA-DRB1 during gestation or shortly after birth is implicated.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
authors.forename: S V
authors.initials: SV
authors.lastname: Ramagopalan
authors.forename: J
authors.initials: J
authors.lastname: Link
authors.forename: J K
authors.initials: JK
authors.lastname: Byrnes
authors.forename: D A
authors.initials: DA
authors.lastname: Dyment
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
authors.forename: R Q
authors.initials: RQ
authors.lastname: Hintzen
authors.forename: E
authors.initials: E
authors.lastname: Sundqvist
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: C
authors.initials: C
authors.lastname: Smestad
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
authors.forename: H F
authors.initials: HF
authors.lastname: Harbo
authors.forename: L
authors.initials: L
authors.lastname: Padyukov
authors.forename: L
authors.initials: L
authors.lastname: Alfredsson
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: A D
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: J
authors.initials: J
authors.lastname: Hillert
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
mesh_terms: D000483:Alleles; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D036801:Parturition; D018570:Risk Assessment; D012307:Risk Factors; D012621:Seasons
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains