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Published on: December 9, 2015
HLA-DRB1 and month of birth in multiple sclerosis
S V Ramagopalan1, J Link, J K Byrnes
1Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
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.
Insights
The month of birth influences multiple sclerosis (MS) risk, particularly for those with the HLA-DRB1*15 gene. This suggests a link between seasonal factors and MS susceptibility genes.
Area of Science:
- Genetics
- Immunology
- Epidemiology
Background:
- Multiple sclerosis (MS) exhibits a month-of-birth effect, with more cases born in spring and fewer in winter.
- This seasonal pattern is more pronounced in familial MS cases.
- The study explores the connection between this birth month effect and the primary MS susceptibility gene, HLA-DRB1.
Purpose of the Study:
- To investigate the association between month of birth and the HLA-DRB1 gene in multiple sclerosis.
- To determine if the principal MS susceptibility gene, HLA-DRB1, influences the observed month-of-birth effect.
Main Methods:
- Genotyping of the HLA-DRB1 gene in 4,834 MS patients, 4,056 controls, and 659 unaffected siblings from Canada, Sweden, and Norway.
- Comparison of birth months between patients, controls, and siblings with and without the HLA-DRB1*15 risk allele.
Main Results:
- Patients with MS carrying the HLA-DRB1*15 risk allele showed significantly fewer November births compared to those without the allele (p=0.02).
- MS patients with HLA-DRB1*15 had more April births than MS patients without this allele (p=0.004).
- These birth month differences were not observed in control groups or unaffected siblings.
Conclusions:
- A significant association exists between month of birth, HLA-DRB1 genotype, and multiple sclerosis risk.
- The findings implicate an interaction between a seasonal environmental factor and genes near or at the HLA-DRB1 locus during early life stages.
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