Lars Alfredsson, PhD, Karolinska Institutet, Stockholm, Sweden, talks on results from two Swedish case-control studies on the environmental interactions in multiple sclerosis (MS) according to human leucocyte antigen (HLA) DRB1*15:01 hetero-homozygosity, as well as three-way interactions between the environmental factors and genetic factors HLA DRB1*15:01 and HLA-A*02. Environmental factors investigated included smoking, EBNA-1 levels, and BMI when young. There was an increased risk of MS in heterozygous individuals compared to those with homozygous HLA DRB1*15:01. Three-way interactions were found between DRB1*15:01, HLA-A*02, and each of the three individual environmental factors, such that smoking, higher EBNA-1 levels, and a high BMI at a young age were associated with much greater risk of MS in those with greater genetic risk. This interview took place at the ACTRIMS Forum 2022 in West Palm Beach, Florida.