RT Journal Article SR Electronic T1 HLA-DRB1 and month of birth in multiple sclerosis JF Neurology JO Neurology FD Lippincott Williams & Wilkins SP 2107 OP 2111 DO 10.1212/WNL.0b013e3181c679f3 VO 73 IS 24 A1 S. V. Ramagopalan A1 J. Link A1 J. K. Byrnes A1 D. A. Dyment A1 G. Giovannoni A1 R. Q. Hintzen A1 E. Sundqvist A1 I. Kockum A1 C. Smestad A1 B. A. Lie A1 H. F. Harbo A1 L. Padyukov A1 L. Alfredsson A1 T. Olsson A1 A. D. Sadovnick A1 J. Hillert A1 G. C. Ebers YR 2009 UL http://n.neurology.org/content/73/24/2107.abstract AB 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. CCPGSMS=Canadian Collaborative Project on the Genetic Susceptibility to Multiple Sclerosis; EIRA=Epidemiologic Investigation of Rheumatoid Arthritis; MHC=major histocompatibility complex; MS=multiple sclerosis; NBMDR=Norwegian Bone Marrow Donor Registry.