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Abstract Details

Environmental exposures associated with Multiple Sclerosis: a UK Biobank study
Multiple Sclerosis
P4 - Poster Session 4 (5:30 PM-6:30 PM)
9-013
To determine environmental risk factors for Multiple Sclerosis (MS) in a large UK cohort.

The estimated heritability of MS is ~40%. There is evidence that the environment (low vitamin D, Epstein-Barr Virus infection, obesity and smoking) affects MS risk; this likely interacts with genetics in determining disease risk.  

We conducted a large case-control study of MS (n=1781) in UK Biobank (n=502,583). A systematic evaluation of all MS-associated exposures was performed. We examined association with MS using logistic regression adjusted for age and gender. Analysis including HLA genotype was restricted to individuals of White ethnicity. Gene-environment interactions were examined by calculating departure from additivity using the Attributable Proportion (AP). 

Higher childhood BMI (‘plumper’ vs ‘thinner’ OR 1.26, 95%CI 1.26-1.66), smoking (current: OR 2.09, 95%CI 1.83-2.38; ex: OR 1.29, 95%CI 1.16-1.43), earlier age at menarche (per year increase in age:  OR 0.93, 95%CI 0.90-0.97), HLA-DRB1*15:01 (heterozygotes OR 2.60, 95%CI 2.35-2.87; homozygotes OR 4.57, 95%CI 3.72-5.55), and lack of HLA-A*02:01 (heterozygotes OR 0.67, 95%CI 0.61-0.75; homozygotes OR 0.61, 95%CI 0.49-0.75) were confirmed as MS risk factors. Month of birth, having been breastfed, maternal smoking, birth weight, male pubertal age, and age at first sexual intercourse were not associated with MS. An interaction was present between childhood BMI and HLA-A*02 (AP 0.25, 95%CI 0.10-0.41), and smoking and HLA DRB1*15:01 (AP  0.14, 95% CI 0.02-0.26). 
This study demonstrates interactions between childhood body size, smoking, and HLA genotype in the UK population. This supports the argument that MS is a results of interactions between genes and environment, helping to identify ‘high-risk’ individuals who may benefit from preventive strategies.
Authors/Disclosures

PRESENTER 		No disclosure on file
Gavin Giovannoni, MD (QMUL) Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
Ruth Dobson (Queen Mary University London) The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Ruth Dobson has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. The institution of Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis . Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sandoz. Ruth Dobson has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Epionex. The institution of Ruth Dobson has received research support from NMSS. The institution of Ruth Dobson has received research support from MS Society UK . The institution of Ruth Dobson has received research support from BMA Foundation . The institution of Ruth Dobson has received research support from Biogen . The institution of Ruth Dobson has received research support from Merck . The institution of Ruth Dobson has received research support from Horne Family Charitable Trust . The institution of Ruth Dobson has received research support from MRC. The institution of Ruth Dobson has received research support from NIHR. Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Medscape . Ruth Dobson has received personal compensation in the range of $0-$499 for serving as a Speaker with Limbus. Ruth Dobson has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Neurology Academy .